[{"article_processing_charge":"No","day":"16","month":"02","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2024.02.15.580289","open_access":"1"}],"citation":{"apa":"Jaeger, E. C. B., Vijatovic, D., Deryckere, A., Zorin, N., Nguyen, A. L., Ivanian, G., … Sweeney, L. B. (n.d.). Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv. https://doi.org/10.1101/2024.02.15.580289","ieee":"E. C. B. Jaeger et al., “Adeno-associated viral tools to trace neural development and connectivity across amphibians,” bioRxiv. .","ista":"Jaeger ECB, Vijatovic D, Deryckere A, Zorin N, Nguyen AL, Ivanian G, Woych J, Arnold RC, Ortega Gurrola A, Shvartsman A, Barbieri F, Toma F-A, Gorbsky GJ, Horb ME, Cline HT, Shay TF, Kelley DB, Yamaguchi A, Shein-Idelson M, Tosches MA, Sweeney LB. Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv, 10.1101/2024.02.15.580289.","ama":"Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv. doi:10.1101/2024.02.15.580289","chicago":"Jaeger, Eliza C.B., David Vijatovic, Astrid Deryckere, Nikol Zorin, Akemi L. Nguyen, Georgiy Ivanian, Jamie Woych, et al. “Adeno-Associated Viral Tools to Trace Neural Development and Connectivity across Amphibians.” BioRxiv, n.d. https://doi.org/10.1101/2024.02.15.580289.","short":"E.C.B. Jaeger, D. Vijatovic, A. Deryckere, N. Zorin, A.L. Nguyen, G. Ivanian, J. Woych, R.C. Arnold, A. Ortega Gurrola, A. Shvartsman, F. Barbieri, F.-A. Toma, G.J. Gorbsky, M.E. Horb, H.T. Cline, T.F. Shay, D.B. Kelley, A. Yamaguchi, M. Shein-Idelson, M.A. Tosches, L.B. Sweeney, BioRxiv (n.d.).","mla":"Jaeger, Eliza C. B., et al. “Adeno-Associated Viral Tools to Trace Neural Development and Connectivity across Amphibians.” BioRxiv, doi:10.1101/2024.02.15.580289."},"publication":"bioRxiv","project":[{"name":"Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während der Metamorphose von Xenopus","grant_number":"FTI21-D-046","_id":"bd73af52-d553-11ed-ba76-912049f0ac7a"},{"grant_number":"101041551","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","name":"Development and Evolution of Tetrapod Motor Circuits"}],"doi":"10.1101/2024.02.15.580289","date_published":"2024-02-16T00:00:00Z","language":[{"iso":"eng"}],"type":"preprint","abstract":[{"text":"The development, evolution, and function of the vertebrate central nervous system (CNS) can be best studied using diverse model organisms. Amphibians, with their unique phylogenetic position at the transition between aquatic and terrestrial lifestyles, are valuable for understanding the origin and evolution of the tetrapod brain and spinal cord. Their metamorphic developmental transitions and unique regenerative abilities also facilitate the discovery of mechanisms for neural circuit remodeling and replacement. The genetic toolkit for amphibians, however, remains limited, with only a few species having sequenced genomes and a small number of transgenic lines available. In mammals, recombinant adeno-associated viral vectors (AAVs) have become a powerful alternative to genome modification for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable neuronal transduction in both developing and adult animals with low toxicity and spatial, temporal, and cell-type specificity. However, AAVs have never been shown to transduce amphibian cells efficiently. To bridge this gap, we established a simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic animals. For each species, we successfully identified at least two AAV serotypes capable of infecting the CNS; however, no pan-amphibian serotype was identified, indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based strategy that targets isochronic cohorts of developing neurons – a critical tool for parsing neural circuit assembly. Finally, to enable visualization and manipulation of neural circuits, we identified AAV variants for retrograde tracing of neuronal projections in adult animals. Our findings expand the toolkit for amphibians to include AAVs, establish a generalizable workflow for AAV screening in non-canonical research organisms, generate testable hypotheses for the evolution of AAV tropism, and lay the foundation for modern cross-species comparisons of vertebrate CNS development, function, and evolution. ","lang":"eng"}],"_id":"15016","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2024","acknowledgement":"We would like to extend our thanks to members of the Sweeney, Tosches, Shein-Idelson,\r\nYamaguchi, Kelley, and Cline Labs for their contributions to this project, discussion and support.\r\nWe additionally thank the Beckman Institute Clover Center and Viviana Gradinaru (Caltech),\r\nKimberly Ritola (UNC NeuroTools), Flavia Gama Gomez Leite (ISTA Viral Core), and Hüseyin\r\nCihan Önal (Shigemoto Group, ISTA) for their consultation and assistance regarding AAVs, as\r\nwell as Andras Simon and Alberto Joven for feedback and discussions on AAVs in Pleurodeles.\r\nTo do these experiments, we have also benefited from the tremendous support of our animal care and imaging facilities at our respective institutions, as well as the amphibian stock centers\r\n(National Xenopus Resource Center, European Xenopus Resource Center, Xenopus Express)\r\nand our funding sources: U.S. National Science Foundation (NSF) Grant Number IOS 2110086\r\n(D.B.K., L.B.S., M.A.T., A.Y., and H.T.C.); United States-Israel Binational Science Foundation\r\n(BSF) Grant Number 2020702 (M.S.-I.); NSF Award Number 1645105 (G.J.G., M.E.H.); FTI\r\nStrategy Lower Austria Dissertation Grant Number FTI21-D-046 (D.V.); Horizon Europe ERC\r\nStarting Grant Number 101041551 (L.B.S.); NIH grant number R35GM146973 (M.A.T.); Rita Allen\r\nFoundation award number GA_032522_FE (M.A.T.); European Molecular Biology Organization\r\nLong-Term Fellowship ALTF 874-2021 (A.D.); National Science Foundation Graduate Research\r\nFellowship DGE 2036197 (E.C.J.B.); NIH grant number P40OD010997 (M.E.H).","department":[{"_id":"LoSw"},{"_id":"MaDe"},{"_id":"GaNo"}],"publication_status":"submitted","status":"public","title":"Adeno-associated viral tools to trace neural development and connectivity across amphibians","author":[{"last_name":"Jaeger","first_name":"Eliza C.B.","full_name":"Jaeger, Eliza C.B."},{"last_name":"Vijatovic","first_name":"David","id":"cf391e77-ec3c-11ea-a124-d69323410b58","full_name":"Vijatovic, David"},{"first_name":"Astrid","last_name":"Deryckere","full_name":"Deryckere, Astrid"},{"full_name":"Zorin, Nikol","first_name":"Nikol","last_name":"Zorin"},{"full_name":"Nguyen, Akemi L.","first_name":"Akemi L.","last_name":"Nguyen"},{"full_name":"Ivanian, Georgiy","last_name":"Ivanian","first_name":"Georgiy","id":"eaf2b366-cfd1-11ee-bbdf-c8790f800a05"},{"full_name":"Woych, Jamie","first_name":"Jamie","last_name":"Woych"},{"full_name":"Arnold, Rebecca C","id":"d6cce458-14c9-11ed-a755-c1c8fc6fde6f","first_name":"Rebecca C","last_name":"Arnold"},{"full_name":"Ortega Gurrola, Alonso","last_name":"Ortega Gurrola","first_name":"Alonso"},{"last_name":"Shvartsman","first_name":"Arik","full_name":"Shvartsman, Arik"},{"first_name":"Francesca","last_name":"Barbieri","id":"a9492887-8972-11ed-ae7b-bfae10998254","full_name":"Barbieri, Francesca"},{"full_name":"Toma, Florina-Alexandra","id":"85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5","last_name":"Toma","first_name":"Florina-Alexandra"},{"full_name":"Gorbsky, Gary J.","last_name":"Gorbsky","first_name":"Gary J."},{"full_name":"Horb, Marko E.","first_name":"Marko E.","last_name":"Horb"},{"full_name":"Cline, Hollis T.","first_name":"Hollis T.","last_name":"Cline"},{"first_name":"Timothy F.","last_name":"Shay","full_name":"Shay, Timothy F."},{"first_name":"Darcy B.","last_name":"Kelley","full_name":"Kelley, Darcy B."},{"first_name":"Ayako","last_name":"Yamaguchi","full_name":"Yamaguchi, Ayako"},{"last_name":"Shein-Idelson","first_name":"Mark","full_name":"Shein-Idelson, Mark"},{"first_name":"Maria Antonietta","last_name":"Tosches","full_name":"Tosches, Maria Antonietta"},{"id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","orcid":"0000-0001-9242-5601","first_name":"Lora Beatrice Jaeger","last_name":"Sweeney","full_name":"Sweeney, Lora Beatrice Jaeger"}],"oa_version":"Preprint","date_updated":"2024-02-20T09:34:25Z","date_created":"2024-02-20T09:20:32Z"},{"article_processing_charge":"No","day":"01","scopus_import":"1","date_published":"2023-10-01T00:00:00Z","page":"1066-1074","article_type":"review","citation":{"ama":"Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 2023;80(10):1066-1074. doi:10.1001/jamapsychiatry.2023.2996","apa":"Schumann, G., Andreassen, O. A., Banaschewski, T., Calhoun, V. D., Clinton, N., Desrivieres, S., … Westlye, L. (2023). Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. American Medical Association. https://doi.org/10.1001/jamapsychiatry.2023.2996","ieee":"G. Schumann et al., “Addressing global environmental challenges to mental health using population neuroscience: A review,” JAMA Psychiatry, vol. 80, no. 10. American Medical Association, pp. 1066–1074, 2023.","ista":"Schumann G, Andreassen OA, Banaschewski T, Calhoun VD, Clinton N, Desrivieres S, Brandlistuen RE, Feng J, Hese S, Hitchen E, Hoffmann P, Jia T, Jirsa V, Marquand AF, Nees F, Nöthen MM, Novarino G, Polemiti E, Ralser M, Rapp M, Schepanski K, Schikowski T, Slater M, Sommer P, Stahl BC, Thompson PM, Twardziok S, Van Der Meer D, Walter H, Westlye L. 2023. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 80(10), 1066–1074.","short":"G. Schumann, O.A. Andreassen, T. Banaschewski, V.D. Calhoun, N. Clinton, S. Desrivieres, R.E. Brandlistuen, J. Feng, S. Hese, E. Hitchen, P. Hoffmann, T. Jia, V. Jirsa, A.F. Marquand, F. Nees, M.M. Nöthen, G. Novarino, E. Polemiti, M. Ralser, M. Rapp, K. Schepanski, T. Schikowski, M. Slater, P. Sommer, B.C. Stahl, P.M. Thompson, S. Twardziok, D. Van Der Meer, H. Walter, L. Westlye, JAMA Psychiatry 80 (2023) 1066–1074.","mla":"Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” JAMA Psychiatry, vol. 80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:10.1001/jamapsychiatry.2023.2996.","chicago":"Schumann, Gunter, Ole A. Andreassen, Tobias Banaschewski, Vince D. Calhoun, Nicholas Clinton, Sylvane Desrivieres, Ragnhild Eek Brandlistuen, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” JAMA Psychiatry. American Medical Association, 2023. https://doi.org/10.1001/jamapsychiatry.2023.2996."},"publication":"JAMA Psychiatry","issue":"10","abstract":[{"lang":"eng","text":"Importance Climate change, pollution, urbanization, socioeconomic inequality, and psychosocial effects of the COVID-19 pandemic have caused massive changes in environmental conditions that affect brain health during the life span, both on a population level as well as on the level of the individual. How these environmental factors influence the brain, behavior, and mental illness is not well known.\r\nObservations A research strategy enabling population neuroscience to contribute to identify brain mechanisms underlying environment-related mental illness by leveraging innovative enrichment tools for data federation, geospatial observation, climate and pollution measures, digital health, and novel data integration techniques is described. This strategy can inform innovative treatments that target causal cognitive and molecular mechanisms of mental illness related to the environment. An example is presented of the environMENTAL Project that is leveraging federated cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress, and substance misuse.\r\nConclusions and Relevance This research will lead to the development of objective biomarkers and evidence-based interventions that will significantly improve outcomes of environment-related mental illness."}],"type":"journal_article","oa_version":"None","intvolume":" 80","status":"public","title":"Addressing global environmental challenges to mental health using population neuroscience: A review","_id":"14443","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["2168-6238"]},"month":"10","language":[{"iso":"eng"}],"doi":"10.1001/jamapsychiatry.2023.2996","quality_controlled":"1","external_id":{"pmid":["37610741"]},"volume":80,"date_updated":"2023-10-31T12:17:20Z","date_created":"2023-10-22T22:01:14Z","author":[{"full_name":"Schumann, Gunter","last_name":"Schumann","first_name":"Gunter"},{"full_name":"Andreassen, Ole A.","first_name":"Ole A.","last_name":"Andreassen"},{"full_name":"Banaschewski, Tobias","first_name":"Tobias","last_name":"Banaschewski"},{"full_name":"Calhoun, Vince D.","first_name":"Vince D.","last_name":"Calhoun"},{"full_name":"Clinton, Nicholas","first_name":"Nicholas","last_name":"Clinton"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, Sylvane"},{"full_name":"Brandlistuen, Ragnhild Eek","last_name":"Brandlistuen","first_name":"Ragnhild Eek"},{"last_name":"Feng","first_name":"Jianfeng","full_name":"Feng, Jianfeng"},{"full_name":"Hese, Soeren","first_name":"Soeren","last_name":"Hese"},{"full_name":"Hitchen, Esther","last_name":"Hitchen","first_name":"Esther"},{"last_name":"Hoffmann","first_name":"Per","full_name":"Hoffmann, Per"},{"full_name":"Jia, Tianye","last_name":"Jia","first_name":"Tianye"},{"last_name":"Jirsa","first_name":"Viktor","full_name":"Jirsa, Viktor"},{"full_name":"Marquand, Andre F.","first_name":"Andre F.","last_name":"Marquand"},{"full_name":"Nees, Frauke","last_name":"Nees","first_name":"Frauke"},{"first_name":"Markus M.","last_name":"Nöthen","full_name":"Nöthen, Markus M."},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Polemiti, Elli","last_name":"Polemiti","first_name":"Elli"},{"full_name":"Ralser, Markus","first_name":"Markus","last_name":"Ralser"},{"full_name":"Rapp, Michael","first_name":"Michael","last_name":"Rapp"},{"first_name":"Kerstin","last_name":"Schepanski","full_name":"Schepanski, Kerstin"},{"full_name":"Schikowski, Tamara","first_name":"Tamara","last_name":"Schikowski"},{"full_name":"Slater, Mel","first_name":"Mel","last_name":"Slater"},{"full_name":"Sommer, Peter","first_name":"Peter","last_name":"Sommer"},{"full_name":"Stahl, Bernd Carsten","first_name":"Bernd Carsten","last_name":"Stahl"},{"first_name":"Paul M.","last_name":"Thompson","full_name":"Thompson, Paul M."},{"full_name":"Twardziok, Sven","last_name":"Twardziok","first_name":"Sven"},{"full_name":"Van Der Meer, Dennis","first_name":"Dennis","last_name":"Van Der Meer"},{"full_name":"Walter, Henrik","first_name":"Henrik","last_name":"Walter"},{"full_name":"Westlye, Lars","last_name":"Westlye","first_name":"Lars"}],"department":[{"_id":"GaNo"}],"publisher":"American Medical Association","publication_status":"published","pmid":1,"year":"2023"},{"volume":29,"date_created":"2023-06-25T22:00:46Z","date_updated":"2023-12-13T11:25:55Z","author":[{"full_name":"Xu, Jiayuan","last_name":"Xu","first_name":"Jiayuan"},{"full_name":"Liu, Nana","last_name":"Liu","first_name":"Nana"},{"full_name":"Polemiti, Elli","first_name":"Elli","last_name":"Polemiti"},{"last_name":"Garcia-Mondragon","first_name":"Liliana","full_name":"Garcia-Mondragon, Liliana"},{"first_name":"Jie","last_name":"Tang","full_name":"Tang, Jie"},{"full_name":"Liu, Xiaoxuan","last_name":"Liu","first_name":"Xiaoxuan"},{"last_name":"Lett","first_name":"Tristram","full_name":"Lett, Tristram"},{"full_name":"Yu, Le","last_name":"Yu","first_name":"Le"},{"full_name":"Nöthen, Markus M.","first_name":"Markus M.","last_name":"Nöthen"},{"last_name":"Feng","first_name":"Jianfeng","full_name":"Feng, Jianfeng"},{"full_name":"Yu, Chunshui","first_name":"Chunshui","last_name":"Yu"},{"full_name":"Marquand, Andre","last_name":"Marquand","first_name":"Andre"},{"full_name":"Schumann, Gunter","last_name":"Schumann","first_name":"Gunter"},{"first_name":"Henrik","last_name":"Walter","full_name":"Walter, Henrik"},{"full_name":"Heinz, Andreas","first_name":"Andreas","last_name":"Heinz"},{"first_name":"Markus","last_name":"Ralser","full_name":"Ralser, Markus"},{"full_name":"Twardziok, Sven","first_name":"Sven","last_name":"Twardziok"},{"last_name":"Vaidya","first_name":"Nilakshi","full_name":"Vaidya, Nilakshi"},{"last_name":"Serin","first_name":"Emin","full_name":"Serin, Emin"},{"last_name":"Jentsch","first_name":"Marcel","full_name":"Jentsch, Marcel"},{"full_name":"Hitchen, Esther","first_name":"Esther","last_name":"Hitchen"},{"first_name":"Roland","last_name":"Eils","full_name":"Eils, Roland"},{"full_name":"Taron, Ulrike Helene","first_name":"Ulrike Helene","last_name":"Taron"},{"first_name":"Tatjana","last_name":"Schütz","full_name":"Schütz, Tatjana"},{"last_name":"Schepanski","first_name":"Kerstin","full_name":"Schepanski, Kerstin"},{"last_name":"Banks","first_name":"Jamie","full_name":"Banks, Jamie"},{"first_name":"Tobias","last_name":"Banaschewski","full_name":"Banaschewski, Tobias"},{"full_name":"Jansone, Karina","first_name":"Karina","last_name":"Jansone"},{"full_name":"Christmann, Nina","first_name":"Nina","last_name":"Christmann"},{"first_name":"Andreas","last_name":"Meyer-Lindenberg","full_name":"Meyer-Lindenberg, Andreas"},{"first_name":"Heike","last_name":"Tost","full_name":"Tost, Heike"},{"full_name":"Holz, Nathalie","last_name":"Holz","first_name":"Nathalie"},{"last_name":"Schwarz","first_name":"Emanuel","full_name":"Schwarz, Emanuel"},{"first_name":"Argyris","last_name":"Stringaris","full_name":"Stringaris, Argyris"},{"full_name":"Neidhart, Maja","first_name":"Maja","last_name":"Neidhart"},{"first_name":"Frauke","last_name":"Nees","full_name":"Nees, Frauke"},{"last_name":"Siehl","first_name":"Sebastian","full_name":"Siehl, Sebastian"},{"full_name":"A. Andreassen, Ole","last_name":"A. Andreassen","first_name":"Ole"},{"full_name":"T. Westlye, Lars","last_name":"T. Westlye","first_name":"Lars"},{"first_name":"Dennis","last_name":"Van Der Meer","full_name":"Van Der Meer, Dennis"},{"first_name":"Sara","last_name":"Fernandez","full_name":"Fernandez, Sara"},{"full_name":"Kjelkenes, Rikka","first_name":"Rikka","last_name":"Kjelkenes"},{"full_name":"Ask, Helga","first_name":"Helga","last_name":"Ask"},{"first_name":"Michael","last_name":"Rapp","full_name":"Rapp, Michael"},{"full_name":"Tschorn, Mira","last_name":"Tschorn","first_name":"Mira"},{"full_name":"Böttger, Sarah Jane","last_name":"Böttger","first_name":"Sarah Jane"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"first_name":"Lena","last_name":"Marr","id":"4406F586-F248-11E8-B48F-1D18A9856A87","full_name":"Marr, Lena"},{"full_name":"Slater, Mel","last_name":"Slater","first_name":"Mel"},{"full_name":"Viapiana, Guillem Feixas","last_name":"Viapiana","first_name":"Guillem Feixas"},{"full_name":"Orosa, Francisco Eiroa","last_name":"Orosa","first_name":"Francisco Eiroa"},{"first_name":"Jaime","last_name":"Gallego","full_name":"Gallego, Jaime"},{"first_name":"Alvaro","last_name":"Pastor","full_name":"Pastor, Alvaro"},{"full_name":"Forstner, Andreas","first_name":"Andreas","last_name":"Forstner"},{"full_name":"Hoffmann, Per","first_name":"Per","last_name":"Hoffmann"},{"full_name":"M. Nöthen, Markus","first_name":"Markus","last_name":"M. Nöthen"},{"first_name":"Andreas","last_name":"J. Forstner","full_name":"J. Forstner, Andreas"},{"full_name":"Claus, Isabelle","first_name":"Isabelle","last_name":"Claus"},{"full_name":"Miller, Abbi","first_name":"Abbi","last_name":"Miller"},{"last_name":"Heilmann-Heimbach","first_name":"Stefanie","full_name":"Heilmann-Heimbach, Stefanie"},{"full_name":"Sommer, Peter","last_name":"Sommer","first_name":"Peter"},{"last_name":"Boye","first_name":"Mona","full_name":"Boye, Mona"},{"last_name":"Wilbertz","first_name":"Johannes","full_name":"Wilbertz, Johannes"},{"first_name":"Karen","last_name":"Schmitt","full_name":"Schmitt, Karen"},{"full_name":"Jirsa, Viktor","first_name":"Viktor","last_name":"Jirsa"},{"first_name":"Spase","last_name":"Petkoski","full_name":"Petkoski, Spase"},{"full_name":"Pitel, Séverine","first_name":"Séverine","last_name":"Pitel"},{"full_name":"Otten, Lisa","last_name":"Otten","first_name":"Lisa"},{"full_name":"Athanasiadis, Anastasios Polykarpos","first_name":"Anastasios Polykarpos","last_name":"Athanasiadis"},{"full_name":"Pearmund, Charlie","last_name":"Pearmund","first_name":"Charlie"},{"first_name":"Bernhard","last_name":"Spanlang","full_name":"Spanlang, Bernhard"},{"last_name":"Alvarez","first_name":"Elena","full_name":"Alvarez, Elena"},{"first_name":"Mavi","last_name":"Sanchez","full_name":"Sanchez, Mavi"},{"full_name":"Giner, Arantxa","first_name":"Arantxa","last_name":"Giner"},{"full_name":"Hese, Sören","last_name":"Hese","first_name":"Sören"},{"first_name":"Paul","last_name":"Renner","full_name":"Renner, Paul"},{"first_name":"Tianye","last_name":"Jia","full_name":"Jia, Tianye"},{"full_name":"Gong, Yanting","last_name":"Gong","first_name":"Yanting"},{"first_name":"Yunman","last_name":"Xia","full_name":"Xia, Yunman"},{"full_name":"Chang, Xiao","first_name":"Xiao","last_name":"Chang"},{"first_name":"Vince","last_name":"Calhoun","full_name":"Calhoun, Vince"},{"full_name":"Liu, Jingyu","first_name":"Jingyu","last_name":"Liu"},{"first_name":"Paul","last_name":"Thompson","full_name":"Thompson, Paul"},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"full_name":"Desrivieres, Sylvane","first_name":"Sylvane","last_name":"Desrivieres"},{"full_name":"H. Young, Allan","first_name":"Allan","last_name":"H. Young"},{"full_name":"Stahl, Bernd","last_name":"Stahl","first_name":"Bernd"},{"first_name":"George","last_name":"Ogoh","full_name":"Ogoh, George"}],"department":[{"_id":"GaNo"}],"publisher":"Springer Nature","publication_status":"published","acknowledgement":"This work received support from the European Union-funded Horizon Europe project ‘environMENTAL’ (no. 101057429 to G.S., A.M. and M.M.N.) and cofunding by UK Research and Innovation under the UK Government’s Horizon Europe funding guarantee (nos. 10041392 and 10038599) for study design and data analysis; the Horizon 2020-funded European Research Council Advanced Grant ‘STRATIFY’ (no. 695313 to G.S. for study design and data analysis); the Human Brain Project (HBP SGA3, no. 945539 to G.S. for study design and data analysis); the National Institutes of Health (grant no. R01DA049238 to G.S. for study design and data analysis); the German Research Foundation (COPE; grant no. 675346 to G.S. for study design and data analysis); the National Natural Science Foundation of China (grant no. 82001797 to J.X., grant no. 82030053 to C.Y., grant no. 82202093 to J.T. and grant no. 82150710554 to G.S. for study design, data analysis and preparation of the manuscript); National Key Research and Development Program of China (grant no. 2018YFC1314301 to C.Y. for study design and data analysis); Tianjin Applied Basic Research Diversified Investment Foundation (grant no. 21JCYBJC01360 to J.X. for study design and data analysis); Tianjin Health Technology Project (grant no. TJWJ2021QN002 to J.X. for preparation of the manuscript); Science & Technology Development Fund of the Tianjin Education Commission for Higher Education (grant no. 2019KJ195 to J.X. for preparation of the manuscript); the Tianjin Medical University ‘Clinical Talent Training 123 Climbing Plan’ to J.X. for the preparation of the manuscript; Tianjin Key Medical Discipline (Specialty) Construction Project (grant no. TJYXZDXK-001A to C.Y. for preparation of the manuscript); the National Key R&D Program of China (grant no. 2022YFE0209400 to L.Y. for study design and data analysis); the Tsinghua University Initiative Scientific Research Program (grant no. 2021Z11GHX002 to L.Y. for study design and data analysis); the National Key Scientific and Technological Infrastructure Project ‘Earth System Science Numerical Simulator Facility’ (EarthLab to L.Y. for study design and data analysis); the Chinese National High-end Foreign Expert Recruitment Plan to G.S.; and the Alexander von Humboldt Foundation to G.S. for study design and data analysis.","year":"2023","file_date_updated":"2023-06-26T10:15:44Z","language":[{"iso":"eng"}],"doi":"10.1038/s41591-023-02365-w","isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["001013172700001"]},"publication_identifier":{"issn":["1078-8956"],"eissn":["1546-170X"]},"month":"06","file":[{"access_level":"open_access","file_name":"2023_NatureMedicine_Xu.pdf","creator":"dernst","file_size":7365360,"content_type":"application/pdf","file_id":"13171","relation":"main_file","success":1,"checksum":"bcd3225b2731c3442fa98987fd3bd46d","date_updated":"2023-06-26T10:15:44Z","date_created":"2023-06-26T10:15:44Z"}],"oa_version":"Published Version","intvolume":" 29","ddc":["570"],"title":"Effects of urban living environments on mental health in adults","status":"public","_id":"13168","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1, explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group (r = 0.10, Pperm < 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3, explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group (r = 0.03, Pperm < 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways.","lang":"eng"}],"type":"journal_article","date_published":"2023-06-15T00:00:00Z","page":"1456-1467","article_type":"original","citation":{"ama":"Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental health in adults. Nature Medicine. 2023;29:1456-1467. doi:10.1038/s41591-023-02365-w","ista":"Xu J, Liu N, Polemiti E, Garcia-Mondragon L, Tang J, Liu X, Lett T, Yu L, Nöthen MM, Feng J, Yu C, Marquand A, Schumann G, Walter H, Heinz A, Ralser M, Twardziok S, Vaidya N, Serin E, Jentsch M, Hitchen E, Eils R, Taron UH, Schütz T, Schepanski K, Banks J, Banaschewski T, Jansone K, Christmann N, Meyer-Lindenberg A, Tost H, Holz N, Schwarz E, Stringaris A, Neidhart M, Nees F, Siehl S, A. Andreassen O, T. Westlye L, Van Der Meer D, Fernandez S, Kjelkenes R, Ask H, Rapp M, Tschorn M, Böttger SJ, Novarino G, Marr L, Slater M, Viapiana GF, Orosa FE, Gallego J, Pastor A, Forstner A, Hoffmann P, M. Nöthen M, J. Forstner A, Claus I, Miller A, Heilmann-Heimbach S, Sommer P, Boye M, Wilbertz J, Schmitt K, Jirsa V, Petkoski S, Pitel S, Otten L, Athanasiadis AP, Pearmund C, Spanlang B, Alvarez E, Sanchez M, Giner A, Hese S, Renner P, Jia T, Gong Y, Xia Y, Chang X, Calhoun V, Liu J, Thompson P, Clinton N, Desrivieres S, H. Young A, Stahl B, Ogoh G. 2023. Effects of urban living environments on mental health in adults. Nature Medicine. 29, 1456–1467.","apa":"Xu, J., Liu, N., Polemiti, E., Garcia-Mondragon, L., Tang, J., Liu, X., … Ogoh, G. (2023). Effects of urban living environments on mental health in adults. Nature Medicine. Springer Nature. https://doi.org/10.1038/s41591-023-02365-w","ieee":"J. Xu et al., “Effects of urban living environments on mental health in adults,” Nature Medicine, vol. 29. Springer Nature, pp. 1456–1467, 2023.","mla":"Xu, Jiayuan, et al. “Effects of Urban Living Environments on Mental Health in Adults.” Nature Medicine, vol. 29, Springer Nature, 2023, pp. 1456–67, doi:10.1038/s41591-023-02365-w.","short":"J. Xu, N. Liu, E. Polemiti, L. Garcia-Mondragon, J. Tang, X. Liu, T. Lett, L. Yu, M.M. Nöthen, J. Feng, C. Yu, A. Marquand, G. Schumann, H. Walter, A. Heinz, M. Ralser, S. Twardziok, N. Vaidya, E. Serin, M. Jentsch, E. Hitchen, R. Eils, U.H. Taron, T. Schütz, K. Schepanski, J. Banks, T. Banaschewski, K. Jansone, N. Christmann, A. Meyer-Lindenberg, H. Tost, N. Holz, E. Schwarz, A. Stringaris, M. Neidhart, F. Nees, S. Siehl, O. A. Andreassen, L. T. Westlye, D. Van Der Meer, S. Fernandez, R. Kjelkenes, H. Ask, M. Rapp, M. Tschorn, S.J. Böttger, G. Novarino, L. Marr, M. Slater, G.F. Viapiana, F.E. Orosa, J. Gallego, A. Pastor, A. Forstner, P. Hoffmann, M. M. Nöthen, A. J. Forstner, I. Claus, A. Miller, S. Heilmann-Heimbach, P. Sommer, M. Boye, J. Wilbertz, K. Schmitt, V. Jirsa, S. Petkoski, S. Pitel, L. Otten, A.P. Athanasiadis, C. Pearmund, B. Spanlang, E. Alvarez, M. Sanchez, A. Giner, S. Hese, P. Renner, T. Jia, Y. Gong, Y. Xia, X. Chang, V. Calhoun, J. Liu, P. Thompson, N. Clinton, S. Desrivieres, A. H. Young, B. Stahl, G. Ogoh, Nature Medicine 29 (2023) 1456–1467.","chicago":"Xu, Jiayuan, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang, Xiaoxuan Liu, Tristram Lett, et al. “Effects of Urban Living Environments on Mental Health in Adults.” Nature Medicine. Springer Nature, 2023. https://doi.org/10.1038/s41591-023-02365-w."},"publication":"Nature Medicine","article_processing_charge":"No","has_accepted_license":"1","day":"15","scopus_import":"1"},{"file_date_updated":"2023-10-30T12:48:40Z","article_number":"1287879","volume":14,"date_created":"2023-10-29T23:01:16Z","date_updated":"2023-12-13T13:06:07Z","author":[{"full_name":"Narzisi, Antonio","first_name":"Antonio","last_name":"Narzisi"},{"last_name":"Halladay","first_name":"Alycia","full_name":"Halladay, Alycia"},{"full_name":"Masi, Gabriele","last_name":"Masi","first_name":"Gabriele"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"first_name":"Catherine","last_name":"Lord","full_name":"Lord, Catherine"}],"publisher":"Frontiers","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"acknowledgement":"The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work has been partially supported by Italian Ministry of Health Grant RC2023 (and the 5 × 1,000 voluntary contributions). The authors thank the children and their families with whom they work daily.","year":"2023","publication_identifier":{"eissn":["1664-0640"]},"month":"10","language":[{"iso":"eng"}],"doi":"10.3389/fpsyt.2023.1287879","isi":1,"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["37854442"],"isi":["001084841700001"]},"type":"journal_article","oa_version":"Published Version","file":[{"file_size":147878,"content_type":"application/pdf","creator":"dernst","file_name":"2023_FrontiersPsychiatry_Narzisi.pdf","access_level":"open_access","date_updated":"2023-10-30T12:48:40Z","date_created":"2023-10-30T12:48:40Z","checksum":"0a76373e9a4c0fc199f80380de257e86","success":1,"relation":"main_file","file_id":"14468"}],"intvolume":" 14","title":"Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment","status":"public","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14455","article_processing_charge":"Yes","has_accepted_license":"1","day":"03","scopus_import":"1","date_published":"2023-10-03T00:00:00Z","article_type":"letter_note","citation":{"ama":"Narzisi A, Halladay A, Masi G, Novarino G, Lord C. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. Frontiers in Psychiatry. 2023;14. doi:10.3389/fpsyt.2023.1287879","apa":"Narzisi, A., Halladay, A., Masi, G., Novarino, G., & Lord, C. (2023). Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. Frontiers in Psychiatry. Frontiers. https://doi.org/10.3389/fpsyt.2023.1287879","ieee":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, and C. Lord, “Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment,” Frontiers in Psychiatry, vol. 14. Frontiers, 2023.","ista":"Narzisi A, Halladay A, Masi G, Novarino G, Lord C. 2023. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. Frontiers in Psychiatry. 14, 1287879.","short":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry 14 (2023).","mla":"Narzisi, Antonio, et al. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” Frontiers in Psychiatry, vol. 14, 1287879, Frontiers, 2023, doi:10.3389/fpsyt.2023.1287879.","chicago":"Narzisi, Antonio, Alycia Halladay, Gabriele Masi, Gaia Novarino, and Catherine Lord. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” Frontiers in Psychiatry. Frontiers, 2023. https://doi.org/10.3389/fpsyt.2023.1287879."},"publication":"Frontiers in Psychiatry"},{"month":"08","publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"doi":"10.1038/s41592-023-01936-6","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"language":[{"iso":"eng"}],"external_id":{"isi":["001025621500001"],"pmid":["37429995"]},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1038/s41592-023-01936-6","open_access":"1"}],"quality_controlled":"1","isi":1,"project":[{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","grant_number":"715767","_id":"24F9549A-B435-11E9-9278-68D0E5697425"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057"}],"ec_funded":1,"author":[{"full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430","first_name":"Eder","last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder"},{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"first_name":"Jake","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake"},{"full_name":"Troidl, Jakob","last_name":"Troidl","first_name":"Jakob"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav","full_name":"Ben Simon, Yoav"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","last_name":"Jahr"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","first_name":"Seth G.N.","full_name":"Grant, Seth G.N."},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"full_name":"Pfister, Hanspeter","first_name":"Hanspeter","last_name":"Pfister"},{"last_name":"Bickel","first_name":"Bernd","orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87","full_name":"Bickel, Bernd"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"}],"related_material":{"record":[{"id":"12817","relation":"research_data","status":"public"},{"id":"14770","relation":"shorter_version","status":"public"}],"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}]},"date_created":"2023-07-23T22:01:13Z","date_updated":"2024-01-10T08:37:48Z","volume":20,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","year":"2023","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"day":"01","article_processing_charge":"Yes","scopus_import":"1","date_published":"2023-08-01T00:00:00Z","publication":"Nature Methods","citation":{"ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6","ieee":"P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6","ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265.","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6."},"article_type":"original","page":"1256-1265","abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"type":"journal_article","oa_version":"Published Version","_id":"13267","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Dense 4D nanoscale reconstruction of living brain tissue","status":"public","intvolume":" 20"},{"oa":1,"project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"doi":"10.15479/at:ista:13107","supervisor":[{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"EM-Fac"}],"degree_awarded":"PhD","language":[{"iso":"eng"}],"month":"05","publication_identifier":{"issn":["2663 - 337X"]},"year":"2023","publication_status":"published","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"publisher":"Institute of Science and Technology Austria","author":[{"full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus"}],"related_material":{"record":[{"id":"12802","relation":"part_of_dissertation","status":"public"}]},"date_updated":"2024-02-07T08:03:33Z","date_created":"2023-06-01T09:05:24Z","file_date_updated":"2023-06-07T08:41:49Z","ec_funded":1,"citation":{"ama":"Knaus L. The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. 2023. doi:10.15479/at:ista:13107","ista":"Knaus L. 2023. The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. Institute of Science and Technology Austria.","ieee":"L. Knaus, “The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival,” Institute of Science and Technology Austria, 2023.","apa":"Knaus, L. (2023). The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13107","mla":"Knaus, Lisa. The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13107.","short":"L. Knaus, The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival, Institute of Science and Technology Austria, 2023.","chicago":"Knaus, Lisa. “The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13107."},"page":"147","date_published":"2023-05-31T00:00:00Z","day":"31","has_accepted_license":"1","article_processing_charge":"No","_id":"13107","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","ddc":["570"],"title":"The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival","status":"public","file":[{"checksum":"4b69a4ac0bbf4163d59c0b58dcb4f2c3","date_created":"2023-06-01T13:48:41Z","date_updated":"2023-06-01T13:48:41Z","file_id":"13112","relation":"source_file","creator":"lknaus","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":12991551,"access_level":"closed","file_name":"Thesis_Lisa Knaus_approved_final.docx"},{"access_level":"open_access","file_name":"Thesis_Lisa Knaus_approved_final_pdfa2b.pdf","file_size":9309015,"content_type":"application/pdf","creator":"lknaus","relation":"main_file","file_id":"13114","checksum":"6903d152aa01181d87a696085af31c83","date_updated":"2023-06-07T08:41:49Z","date_created":"2023-06-02T09:47:29Z"}],"oa_version":"Published Version","type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"text":"Within the human body, the brain exhibits the highest rate of energy consumption amongst all organs, with the majority of generated ATP being utilized to sustain neuronal activity. Therefore, the metabolism of the mature cerebral cortex is geared towards preserving metabolic homeostasis whilst generating significant amounts of energy. This requires a precise interplay between diverse metabolic pathways, spanning from a tissue-wide scale to the level of individual neurons. Disturbances to this delicate metabolic equilibrium, such as those resulting from maternal malnutrition\r\nor mutations affecting metabolic enzymes, often result in neuropathological variants of neurodevelopment. For instance, mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), have been associated with autism and microcephaly. However, despite recent progress in the field, the extent of metabolic restructuring that occurs within the developing brain and the corresponding alterations in nutrient demands during various critical periods remain largely unknown. To investigate this, we performed metabolomic profiling of the murine cerebral cortex to characterize the metabolic state of the forebrain at different developmental stages. We found that the developing cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites displaying stage-specific changes. According to our observations, we determined a distinct temporal period in postnatal development during which the cortex displays heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model, we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed neuronal metabolic state across multiple developmental stages of corticogenesis. We found that manipulating the levels of essential LNAAs in cortical neurons in vivo affects one particular perinatal developmental period critical for cortical network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous alterations in neuronal lipid metabolism, excitability, and survival during this particular time window. Although most of the effects of Slc7a5 deletion on neuronal physiology are transient, derailment of these processes during this brief but crucial window leads to long-term circuit dysfunction in mice. In conclusion, out data indicate that the cerebral cortex undergoes significant metabolic reorganization during development. This process involves the intricate integration of multiple metabolic pathways to ensure optimal neuronal function throughout different developmental stages. Our findings offer a paradigm for understanding how neurons synchronize the expression of nutrient-related genes with their activity to allow proper brain maturation. Further, our results demonstrate that disruptions in these precisely calibrated metabolic processes during critical periods of brain development may result in neuropathological outcomes in mice and in humans.","lang":"eng"}]},{"month":"04","publication_identifier":{"issn":["0092-8674"]},"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2023.02.037","quality_controlled":"1","isi":1,"project":[{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000991468700001"]},"file_date_updated":"2023-05-02T09:26:21Z","ec_funded":1,"date_updated":"2024-02-07T08:03:32Z","date_created":"2023-04-05T08:15:40Z","volume":186,"author":[{"full_name":"Knaus, Lisa","first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Basilico, Bernadette","last_name":"Basilico","first_name":"Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Malzl","first_name":"Daniel","full_name":"Malzl, Daniel"},{"full_name":"Gerykova Bujalkova, Maria","first_name":"Maria","last_name":"Gerykova Bujalkova"},{"last_name":"Smogavec","first_name":"Mateja","full_name":"Smogavec, Mateja"},{"last_name":"Schwarz","first_name":"Lena A.","full_name":"Schwarz, Lena A."},{"id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz","first_name":"Sarah","full_name":"Gorkiewicz, Sarah"},{"full_name":"Amberg, Nicole","last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian"},{"last_name":"Knittl-Frank","first_name":"Christian","full_name":"Knittl-Frank, Christian"},{"id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","first_name":"Marianna","last_name":"Tassinari","full_name":"Tassinari, Marianna"},{"full_name":"Maulide, Nuno","last_name":"Maulide","first_name":"Nuno"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"full_name":"Menche, Jörg","first_name":"Jörg","last_name":"Menche"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"related_material":{"link":[{"relation":"press_release","description":"News on ISTA Website","url":"https://ista.ac.at/en/news/feed-them-or-lose-them/"}],"record":[{"relation":"dissertation_contains","status":"public","id":"13107"}]},"publication_status":"published","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"publisher":"Elsevier","acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","year":"2023","day":"27","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","keyword":["General Biochemistry","Genetics and Molecular Biology"],"scopus_import":"1","date_published":"2023-04-27T00:00:00Z","article_type":"original","page":"1950-1967.e25","publication":"Cell","citation":{"mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:10.1016/j.cell.2023.02.037.","short":"L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier, 2023. https://doi.org/10.1016/j.cell.2023.02.037.","ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037","ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","apa":"Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037","ieee":"L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023."},"abstract":[{"lang":"eng","text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction."}],"issue":"9","type":"journal_article","oa_version":"Published Version","file":[{"success":1,"checksum":"47e94fbe19e86505b429cb7a5b503ce6","date_created":"2023-05-02T09:26:21Z","date_updated":"2023-05-02T09:26:21Z","file_id":"12889","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":15712841,"access_level":"open_access","file_name":"2023_Cell_Knaus.pdf"}],"status":"public","title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","ddc":["570"],"intvolume":" 186","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12802"},{"oa_version":"Published Version","title":"Imaging brain tissue architecture across millimeter to nanometer scales","status":"public","_id":"14257","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"type":"journal_article","date_published":"2023-08-31T00:00:00Z","article_type":"original","publication":"Nature Biotechnology","citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8","ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8"},"day":"31","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","date_created":"2023-09-03T22:01:15Z","date_updated":"2024-02-21T12:18:18Z","author":[{"full_name":"Michalska, Julia M","last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"full_name":"Velicky, Philipp","last_name":"Velicky","first_name":"Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","last_name":"Korinkova"},{"full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson"},{"full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","first_name":"Nicole"},{"orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","first_name":"Alessandro","full_name":"Venturino, Alessandro"},{"first_name":"Karl","last_name":"Roessler","full_name":"Roessler, Karl"},{"last_name":"Czech","first_name":"Thomas","full_name":"Czech, Thomas"},{"last_name":"Höftberger","first_name":"Romana","full_name":"Höftberger, Romana"},{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"}],"related_material":{"record":[{"id":"13126","status":"public","relation":"research_data"}],"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}]},"publication_status":"epub_ahead","publisher":"Springer Nature","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","year":"2023","ec_funded":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41587-023-01911-8","isi":1,"quality_controlled":"1","project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"The Wittgenstein Prize","call_identifier":"FWF"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry"}],"main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"external_id":{"isi":["001065254200001"]},"oa":1,"month":"08","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]}},{"intvolume":" 16","title":"What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior","status":"public","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12140","file":[{"file_name":"2022_FrontiersNeuroscience_Basilico.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":6399987,"file_id":"12352","relation":"main_file","date_created":"2023-01-24T09:16:29Z","date_updated":"2023-01-24T09:16:29Z","success":1,"checksum":"84696213ecf99182c58a9f34b9ff2e23"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Microglia are dynamic cells, constantly surveying their surroundings and interacting with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical role of microglia in modulating synaptic transmission and plasticity in the developing brain. In the past decade, novel pharmacological and genetic strategies have allowed the acute removal of microglia, opening the possibility to explore and understand the role of microglia also in the adult brain. In this review, we summarized and discussed the contribution of microglia depletion strategies to the current understanding of the role of microglia on synaptic function, learning and memory, and behavior both in physiological and pathological conditions. We first described the available microglia depletion methods highlighting their main strengths and weaknesses. We then reviewed the impact of microglia depletion on structural and functional synaptic plasticity. Next, we focused our analysis on the effects of microglia depletion on behavior, including general locomotor activity, sensory perception, motor function, sociability, learning and memory both in healthy animals and animal models of disease. Finally, we integrated the findings from the reviewed studies and discussed the emerging roles of microglia on the maintenance of synaptic function, learning, memory strength and forgetfulness, and the implications of microglia depletion in models of brain disease."}],"article_type":"original","citation":{"chicago":"Basilico, Bernadette, Laura Ferrucci, Azka Khan, Silvia Di Angelantonio, Davide Ragozzino, and Ingrid Reverte. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular Neuroscience. Frontiers Media, 2022. https://doi.org/10.3389/fncel.2022.1022431.","short":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte, Frontiers in Cellular Neuroscience 16 (2022).","mla":"Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular Neuroscience, vol. 16, 1022431, Frontiers Media, 2022, doi:10.3389/fncel.2022.1022431.","apa":"Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., & Reverte, I. (2022). What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2022.1022431","ieee":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, and I. Reverte, “What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior,” Frontiers in Cellular Neuroscience, vol. 16. Frontiers Media, 2022.","ista":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. 2022. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 16, 1022431.","ama":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 2022;16. doi:10.3389/fncel.2022.1022431"},"publication":"Frontiers in Cellular Neuroscience","date_published":"2022-11-04T00:00:00Z","keyword":["Cellular and Molecular Neuroscience"],"scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"04","publisher":"Frontiers Media","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"acknowledgement":"The write-up of the review was supported by Sapienza University of Rome (Fondi di Ateneo, grant numbers #MA32117A7B698029 and #PH12017270934C3C to SD), Regione Lazio (POR FSE 2014/20, grant number #19036AP000000019 to SD), Fulbright 2019 (grant number\r\n#FSP-P005556 to SD), Institute Pasteur Italia (Fondi Cenci Bolognetti #363 to DR), and Network of European Funding for Neuroscience Research (ERA-NET NEURON Transnational\r\nResearch Projects on Neurodevelopmental Disorders 2021, grant acronym #JTC2021-SHANKAstro to DR).","year":"2022","volume":16,"date_created":"2023-01-12T12:04:50Z","date_updated":"2023-08-04T08:56:10Z","author":[{"orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"full_name":"Ferrucci, Laura","first_name":"Laura","last_name":"Ferrucci"},{"last_name":"Khan","first_name":"Azka","full_name":"Khan, Azka"},{"first_name":"Silvia","last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia"},{"last_name":"Ragozzino","first_name":"Davide","full_name":"Ragozzino, Davide"},{"full_name":"Reverte, Ingrid","last_name":"Reverte","first_name":"Ingrid"}],"article_number":"1022431","file_date_updated":"2023-01-24T09:16:29Z","quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000886526600001"],"pmid":["36406752"]},"language":[{"iso":"eng"}],"doi":"10.3389/fncel.2022.1022431","publication_identifier":{"issn":["1662-5102"]},"month":"11"},{"author":[{"full_name":"Guerrini, Renzo","first_name":"Renzo","last_name":"Guerrini"},{"full_name":"Mei, Davide","first_name":"Davide","last_name":"Mei"},{"first_name":"Margit Katalin","last_name":"Szigeti","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9500-8758","full_name":"Szigeti, Margit Katalin"},{"first_name":"Sara","last_name":"Pepe","full_name":"Pepe, Sara"},{"last_name":"Koenig","first_name":"Mary Kay","full_name":"Koenig, Mary Kay"},{"last_name":"Von Allmen","first_name":"Gretchen","full_name":"Von Allmen, Gretchen"},{"full_name":"Cho, Megan T","last_name":"Cho","first_name":"Megan T"},{"last_name":"McDonald","first_name":"Kimberly","full_name":"McDonald, Kimberly"},{"full_name":"Baker, Janice","first_name":"Janice","last_name":"Baker"},{"full_name":"Bhambhani, Vikas","first_name":"Vikas","last_name":"Bhambhani"},{"full_name":"Powis, Zöe","first_name":"Zöe","last_name":"Powis"},{"first_name":"Lance","last_name":"Rodan","full_name":"Rodan, Lance"},{"first_name":"Rima","last_name":"Nabbout","full_name":"Nabbout, Rima"},{"last_name":"Barcia","first_name":"Giulia","full_name":"Barcia, Giulia"},{"full_name":"Rosenfeld, Jill A","first_name":"Jill A","last_name":"Rosenfeld"},{"full_name":"Bacino, Carlos A","first_name":"Carlos A","last_name":"Bacino"},{"last_name":"Mignot","first_name":"Cyril","full_name":"Mignot, Cyril"},{"last_name":"Power","first_name":"Lillian H","full_name":"Power, Lillian H"},{"full_name":"Harris, Catharine J","first_name":"Catharine J","last_name":"Harris"},{"first_name":"Dragan","last_name":"Marjanovic","full_name":"Marjanovic, Dragan"},{"full_name":"Møller, Rikke S","first_name":"Rikke S","last_name":"Møller"},{"full_name":"Hammer, Trine B","last_name":"Hammer","first_name":"Trine B"},{"last_name":"Keski Filppula","first_name":"Riikka","full_name":"Keski Filppula, Riikka"},{"first_name":"Päivi","last_name":"Vieira","full_name":"Vieira, Päivi"},{"first_name":"Clara","last_name":"Hildebrandt","full_name":"Hildebrandt, Clara"},{"first_name":"Stephanie","last_name":"Sacharow","full_name":"Sacharow, Stephanie"},{"full_name":"Maragliano, Luca","last_name":"Maragliano","first_name":"Luca"},{"full_name":"Benfenati, Fabio","last_name":"Benfenati","first_name":"Fabio"},{"first_name":"Katherine","last_name":"Lachlan","full_name":"Lachlan, Katherine"},{"full_name":"Benneche, Andreas","last_name":"Benneche","first_name":"Andreas"},{"full_name":"Petit, Florence","last_name":"Petit","first_name":"Florence"},{"full_name":"de Sainte Agathe, Jean Madeleine","first_name":"Jean Madeleine","last_name":"de Sainte Agathe"},{"full_name":"Hallinan, Barbara","last_name":"Hallinan","first_name":"Barbara"},{"first_name":"Yue","last_name":"Si","full_name":"Si, Yue"},{"full_name":"Wentzensen, Ingrid M","first_name":"Ingrid M","last_name":"Wentzensen"},{"full_name":"Zou, Fanggeng","first_name":"Fanggeng","last_name":"Zou"},{"first_name":"Vinodh","last_name":"Narayanan","full_name":"Narayanan, Vinodh"},{"last_name":"Matsumoto","first_name":"Naomichi","full_name":"Matsumoto, Naomichi"},{"first_name":"Alessandra","last_name":"Boncristiano","full_name":"Boncristiano, Alessandra"},{"full_name":"la Marca, Giancarlo","first_name":"Giancarlo","last_name":"la Marca"},{"full_name":"Kato, Mitsuhiro","first_name":"Mitsuhiro","last_name":"Kato"},{"last_name":"Anderson","first_name":"Kristin","full_name":"Anderson, Kristin"},{"first_name":"Carmen","last_name":"Barba","full_name":"Barba, Carmen"},{"full_name":"Sturiale, Luisa","last_name":"Sturiale","first_name":"Luisa"},{"full_name":"Garozzo, Domenico","first_name":"Domenico","last_name":"Garozzo"},{"full_name":"Bei, Roberto","last_name":"Bei","first_name":"Roberto"},{"last_name":"Masuelli","first_name":"Laura","full_name":"Masuelli, Laura"},{"last_name":"Conti","first_name":"Valerio","full_name":"Conti, Valerio"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"last_name":"Fassio","first_name":"Anna","full_name":"Fassio, Anna"}],"volume":145,"date_updated":"2023-08-04T09:13:08Z","date_created":"2023-01-12T12:11:45Z","acknowledgement":"We thank all patients and family members for their participation in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria) for generating the human iPSC lines and\r\nfor performing quality checks. We thank Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen preparation for transmission electron microscopy and Flavia Leite for preparing the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology Services at IST Austria is greatly acknowledged. We would like to thank Doctors Jane Hurst and Richard Scott for their help in retrieving the detailed clinical information of Patient 17. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic information on Patient 23 was made available through access to the data and findings generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.). \r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018 (grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex epilepsies (EpiCARE) provided financial support for meetings organization. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication\r\nare those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org), which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. ","year":"2022","department":[{"_id":"GaNo"}],"publisher":"Oxford University Press","publication_status":"published","ec_funded":1,"doi":"10.1093/brain/awac145","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"external_id":{"isi":["000807770000001"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/brain/awac145"}],"oa":1,"project":[{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"isi":1,"quality_controlled":"1","publication_identifier":{"issn":["0006-8950"],"eissn":["1460-2156"]},"month":"08","oa_version":"Published Version","_id":"12174","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 145","status":"public","title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","issue":"8","abstract":[{"text":"Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.\r\n Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes.\r\nATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants.","lang":"eng"}],"type":"journal_article","date_published":"2022-08-01T00:00:00Z","citation":{"mla":"Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain, vol. 145, no. 8, Oxford University Press, 2022, pp. 2687–703, doi:10.1093/brain/awac145.","short":"R. Guerrini, D. Mei, M.K. Szigeti, S. Pepe, M.K. Koenig, G. Von Allmen, M.T. Cho, K. McDonald, J. Baker, V. Bhambhani, Z. Powis, L. Rodan, R. Nabbout, G. Barcia, J.A. Rosenfeld, C.A. Bacino, C. Mignot, L.H. Power, C.J. Harris, D. Marjanovic, R.S. Møller, T.B. Hammer, R. Keski Filppula, P. Vieira, C. Hildebrandt, S. Sacharow, L. Maragliano, F. Benfenati, K. Lachlan, A. Benneche, F. Petit, J.M. de Sainte Agathe, B. Hallinan, Y. Si, I.M. Wentzensen, F. Zou, V. Narayanan, N. Matsumoto, A. Boncristiano, G. la Marca, M. Kato, K. Anderson, C. Barba, L. Sturiale, D. Garozzo, R. Bei, L. Masuelli, V. Conti, G. Novarino, A. Fassio, Brain 145 (2022) 2687–2703.","chicago":"Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain. Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145.","ama":"Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 2022;145(8):2687-2703. doi:10.1093/brain/awac145","ista":"Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 145(8), 2687–2703.","ieee":"R. Guerrini et al., “Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis,” Brain, vol. 145, no. 8. Oxford University Press, pp. 2687–2703, 2022.","apa":"Guerrini, R., Mei, D., Szigeti, M. K., Pepe, S., Koenig, M. K., Von Allmen, G., … Fassio, A. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. Oxford University Press. https://doi.org/10.1093/brain/awac145"},"publication":"Brain","page":"2687-2703","article_type":"original","article_processing_charge":"No","day":"01","scopus_import":"1","keyword":["Neurology (clinical)"]},{"file":[{"date_created":"2023-01-30T10:25:21Z","date_updated":"2023-01-30T10:25:21Z","checksum":"efc7edf9f626af31853790c5b598a68c","success":1,"relation":"main_file","file_id":"12450","content_type":"application/pdf","file_size":13588502,"creator":"dernst","file_name":"2022_FrontiersOntology_Basilico.pdf","access_level":"open_access"}],"oa_version":"Published Version","intvolume":" 12","title":"Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells","ddc":["570"],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12268","abstract":[{"text":"The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment.","lang":"eng"}],"type":"journal_article","date_published":"2022-08-25T00:00:00Z","article_type":"original","citation":{"ama":"Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.983507","ista":"Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B. 2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.","ieee":"B. Basilico et al., “Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells,” Frontiers in Oncology, vol. 12. Frontiers Media, 2022.","apa":"Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M., … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. Frontiers Media. https://doi.org/10.3389/fonc.2022.983507","mla":"Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology, vol. 12, 983507, Frontiers Media, 2022, doi:10.3389/fonc.2022.983507.","short":"B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P. Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione, G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).","chicago":"Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro, Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology. Frontiers Media, 2022. https://doi.org/10.3389/fonc.2022.983507."},"publication":"Frontiers in Oncology","article_processing_charge":"No","has_accepted_license":"1","day":"25","keyword":["Cancer Research","Oncology"],"scopus_import":"1","volume":12,"date_updated":"2023-08-04T09:54:16Z","date_created":"2023-01-16T10:00:28Z","author":[{"full_name":"Basilico, Bernadette","first_name":"Bernadette","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173"},{"full_name":"Palamà, Ilaria Elena","last_name":"Palamà","first_name":"Ilaria Elena"},{"full_name":"D’Amone, Stefania","first_name":"Stefania","last_name":"D’Amone"},{"last_name":"Lauro","first_name":"Clotilde","full_name":"Lauro, Clotilde"},{"full_name":"Rosito, Maria","first_name":"Maria","last_name":"Rosito"},{"full_name":"Grieco, Maddalena","last_name":"Grieco","first_name":"Maddalena"},{"full_name":"Ratano, Patrizia","last_name":"Ratano","first_name":"Patrizia"},{"first_name":"Federica","last_name":"Cordella","full_name":"Cordella, Federica"},{"full_name":"Sanchini, Caterina","first_name":"Caterina","last_name":"Sanchini"},{"last_name":"Di Angelantonio","first_name":"Silvia","full_name":"Di Angelantonio, Silvia"},{"first_name":"Davide","last_name":"Ragozzino","full_name":"Ragozzino, Davide"},{"last_name":"Cascione","first_name":"Mariafrancesca","full_name":"Cascione, Mariafrancesca"},{"first_name":"Giuseppe","last_name":"Gigli","full_name":"Gigli, Giuseppe"},{"full_name":"Cortese, Barbara","last_name":"Cortese","first_name":"Barbara"}],"department":[{"_id":"GaNo"}],"publisher":"Frontiers Media","publication_status":"published","pmid":1,"year":"2022","acknowledgement":"The research leading to these results has received funding from AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG 2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia: DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela Marchetti for practical administrative support.","file_date_updated":"2023-01-30T10:25:21Z","article_number":"983507","language":[{"iso":"eng"}],"doi":"10.3389/fonc.2022.983507","quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000856524900001"],"pmid":["36091138"]},"publication_identifier":{"issn":["2234-943X"]},"month":"08"},{"type":"journal_article","abstract":[{"lang":"eng","text":"Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses."}],"issue":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"10818","ddc":["570"],"title":"Microglia control glutamatergic synapses in the adult mouse hippocampus","status":"public","intvolume":" 70","oa_version":"Published Version","file":[{"success":1,"checksum":"f10a897290e66c0a062e04ba91db6c17","date_updated":"2022-03-04T08:55:27Z","date_created":"2022-03-04T08:55:27Z","file_id":"10819","relation":"main_file","creator":"dernst","file_size":5340294,"content_type":"application/pdf","access_level":"open_access","file_name":"2021_Glia_Basilico.pdf"}],"scopus_import":"1","keyword":["Cellular and Molecular Neuroscience","Neurology"],"day":"01","has_accepted_license":"1","article_processing_charge":"No","publication":"Glia","citation":{"mla":"Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia, vol. 70, no. 1, Wiley, 2022, pp. 173–95, doi:10.1002/glia.24101.","short":"B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito, V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris, D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi, M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L. Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195.","chicago":"Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia, Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia. Wiley, 2022. https://doi.org/10.1002/glia.24101.","ama":"Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 2022;70(1):173-195. doi:10.1002/glia.24101","ista":"Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 70(1), 173–195.","ieee":"B. Basilico et al., “Microglia control glutamatergic synapses in the adult mouse hippocampus,” Glia, vol. 70, no. 1. Wiley, pp. 173–195, 2022.","apa":"Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. Wiley. https://doi.org/10.1002/glia.24101"},"article_type":"original","page":"173-195","date_published":"2022-01-01T00:00:00Z","file_date_updated":"2022-03-04T08:55:27Z","year":"2022","acknowledgement":"The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003) to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University, Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza University, Rome and by the Italian Institute of Technology, Rome. The authors thank Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani for help with animal husbandry and transgenic colonies management. They also wish to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism. PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley, CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.","pmid":1,"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Wiley","author":[{"orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"first_name":"Laura","last_name":"Ferrucci","full_name":"Ferrucci, Laura"},{"last_name":"Ratano","first_name":"Patrizia","full_name":"Ratano, Patrizia"},{"full_name":"Golia, Maria T.","last_name":"Golia","first_name":"Maria T."},{"first_name":"Alfonso","last_name":"Grimaldi","full_name":"Grimaldi, Alfonso"},{"last_name":"Rosito","first_name":"Maria","full_name":"Rosito, Maria"},{"first_name":"Valentina","last_name":"Ferretti","full_name":"Ferretti, Valentina"},{"first_name":"Ingrid","last_name":"Reverte","full_name":"Reverte, Ingrid"},{"first_name":"Caterina","last_name":"Sanchini","full_name":"Sanchini, Caterina"},{"full_name":"Marrone, Maria C.","last_name":"Marrone","first_name":"Maria C."},{"first_name":"Maria","last_name":"Giubettini","full_name":"Giubettini, Maria"},{"full_name":"De Turris, Valeria","last_name":"De Turris","first_name":"Valeria"},{"last_name":"Salerno","first_name":"Debora","full_name":"Salerno, Debora"},{"full_name":"Garofalo, Stefano","first_name":"Stefano","last_name":"Garofalo"},{"full_name":"St‐Pierre, Marie‐Kim","last_name":"St‐Pierre","first_name":"Marie‐Kim"},{"full_name":"Carrier, Micael","first_name":"Micael","last_name":"Carrier"},{"first_name":"Massimiliano","last_name":"Renzi","full_name":"Renzi, Massimiliano"},{"first_name":"Francesca","last_name":"Pagani","full_name":"Pagani, Francesca"},{"full_name":"Modi, Brijesh","first_name":"Brijesh","last_name":"Modi"},{"last_name":"Raspa","first_name":"Marcello","full_name":"Raspa, Marcello"},{"last_name":"Scavizzi","first_name":"Ferdinando","full_name":"Scavizzi, Ferdinando"},{"first_name":"Cornelius T.","last_name":"Gross","full_name":"Gross, Cornelius T."},{"full_name":"Marinelli, Silvia","last_name":"Marinelli","first_name":"Silvia"},{"full_name":"Tremblay, Marie‐Ève","last_name":"Tremblay","first_name":"Marie‐Ève"},{"full_name":"Caprioli, Daniele","first_name":"Daniele","last_name":"Caprioli"},{"last_name":"Maggi","first_name":"Laura","full_name":"Maggi, Laura"},{"full_name":"Limatola, Cristina","last_name":"Limatola","first_name":"Cristina"},{"full_name":"Di Angelantonio, Silvia","first_name":"Silvia","last_name":"Di Angelantonio"},{"full_name":"Ragozzino, Davide","last_name":"Ragozzino","first_name":"Davide"}],"date_created":"2022-03-04T08:53:37Z","date_updated":"2023-09-05T16:01:23Z","volume":70,"month":"01","publication_identifier":{"eissn":["1098-1136"],"issn":["0894-1491"]},"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"external_id":{"pmid":["34661306"],"isi":["000708025800001"]},"isi":1,"quality_controlled":"1","doi":"10.1002/glia.24101","language":[{"iso":"eng"}]},{"oa_version":"Preprint","date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-23T11:07:59Z","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"author":[{"full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430","first_name":"Eder","last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder"},{"full_name":"Michalska, Julia M","first_name":"Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"last_name":"Lin","first_name":"Zudi","full_name":"Lin, Zudi"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Wiebke","last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"full_name":"Grant, Seth G. N.","first_name":"Seth G. N.","last_name":"Grant"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Pfister","first_name":"Hanspeter","full_name":"Pfister, Hanspeter"},{"orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","first_name":"Bernd","full_name":"Bickel, Bernd"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"}],"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","title":"Saturated reconstruction of living brain tissue","publication_status":"submitted","status":"public","year":"2022","_id":"11943","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue.","lang":"eng"}],"type":"preprint","language":[{"iso":"eng"}],"date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.03.16.484431"}],"citation":{"ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.)."},"publication":"bioRxiv","article_processing_charge":"No","day":"09","month":"05"},{"citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272","ieee":"J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"oa":1,"publication":"bioRxiv","language":[{"iso":"eng"}],"doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","article_processing_charge":"No","day":"18","month":"08","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","publication_status":"submitted","status":"public","_id":"11950","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-24T08:24:52Z","related_material":{"record":[{"id":"12470","relation":"dissertation_contains","status":"public"}]},"author":[{"last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M"},{"full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Velicky, Philipp","last_name":"Velicky","first_name":"Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","first_name":"Hana","full_name":"Korinkova, Hana"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"}],"type":"preprint","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons."}]},{"publication_identifier":{"issn":["2211-1247"]},"month":"04","doi":"10.1016/j.celrep.2022.110615","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF"}],"quality_controlled":"1","isi":1,"ec_funded":1,"file_date_updated":"2022-04-15T09:06:25Z","article_number":"110615","related_material":{"record":[{"id":"12364","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"first_name":"Cristina","last_name":"Cheroni","full_name":"Cheroni, Cristina"},{"first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"full_name":"Sacco, Roberto","first_name":"Roberto","last_name":"Sacco","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","last_name":"Yahya","first_name":"Aysan Çerağ"},{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gabriele","first_name":"Michele","full_name":"Gabriele, Michele"},{"orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia","full_name":"Lyudchik, Julia"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"full_name":"Gabitto, Mariano","first_name":"Mariano","last_name":"Gabitto"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"},{"last_name":"Testa","first_name":"Giuseppe","full_name":"Testa, Giuseppe"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"volume":39,"date_updated":"2024-03-28T23:30:45Z","date_created":"2022-04-15T09:03:10Z","pmid":1,"acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","year":"2022","publisher":"Elsevier","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"publication_status":"published","has_accepted_license":"1","article_processing_charge":"Yes","day":"05","keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_published":"2022-04-05T00:00:00Z","citation":{"ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615","ieee":"C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615."},"publication":"Cell Reports","article_type":"original","issue":"1","abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"type":"journal_article","file":[{"checksum":"b4e8d68f0268dec499af333e6fd5d8e1","success":1,"date_created":"2022-04-15T09:06:25Z","date_updated":"2022-04-15T09:06:25Z","relation":"main_file","file_id":"11164","content_type":"application/pdf","file_size":"7808644","creator":"dernst","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf"}],"oa_version":"Published Version","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"11160","intvolume":" 39","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","status":"public","ddc":["570"]},{"publication_identifier":{"issn":["2663-337X"]},"month":"09","project":[{"name":"Probing development and reversibility of autism spectrum disorders","grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF"}],"oa":1,"language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"doi":"10.15479/at:ista:12094","ec_funded":1,"file_date_updated":"2023-09-20T22:30:03Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"publication_status":"published","year":"2022","date_created":"2023-01-24T13:09:57Z","date_updated":"2023-11-16T13:10:22Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"3"},{"status":"public","relation":"part_of_dissertation","id":"11160"}]},"author":[{"full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph"}],"article_processing_charge":"No","has_accepted_license":"1","day":"19","page":"152","citation":{"chicago":"Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12094.","short":"C. Dotter, Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.","mla":"Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12094.","ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.","apa":"Dotter, C. (2022). Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12094","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria.","ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094"},"date_published":"2022-09-19T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"text":"Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders character\u0002ized by behavioral symptoms such as problems in social communication and interaction, as\r\nwell as repetitive, restricted behaviors and interests. These disorders show a high degree\r\nof heritability and hundreds of risk genes have been identifed using high throughput\r\nsequencing technologies. This genetic heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD but at the same time given rise to the concept of convergent\r\nmechanisms. Previous studies have identifed that risk genes for ASD broadly converge\r\nonto specifc functional categories with transcriptional regulation being one of the biggest\r\ngroups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing. While the former\r\nwere generated earlier in CHD8+/- organoids, the generation of the latter was shifted to\r\nlater times in favor of a prolonged progenitor expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral ganglionic eminence. As this project is still ongoing at the time of writing, future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying this shift with\r\nthe aim of linking these three ASD risk genes through biological convergence.","lang":"eng"}],"status":"public","title":"Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder","ddc":["570"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","_id":"12364","file":[{"relation":"main_file","embargo":"2023-09-19","file_id":"12365","date_created":"2023-01-24T13:15:45Z","date_updated":"2023-09-20T22:30:03Z","checksum":"896f4cac9adb6d3f26a6605772f4e1a3","file_name":"220923_Thesis_CDotter_Final.pdf","access_level":"open_access","file_size":20457465,"content_type":"application/pdf","creator":"cchlebak"},{"relation":"source_file","file_id":"12482","date_updated":"2023-09-20T22:30:03Z","date_created":"2023-02-02T09:15:35Z","checksum":"ad01bb20da163be6893b7af832e58419","embargo_to":"open_access","file_name":"latex_source_CDotter_Thesis_2022.zip","access_level":"closed","file_size":22433512,"content_type":"application/x-zip-compressed","creator":"cchlebak"}],"oa_version":"Published Version"},{"publication":"Genes","citation":{"ieee":"V. Vasic et al., “Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment,” Genes, vol. 12, no. 11. MDPI, 2021.","apa":"Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino, G., & Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. MDPI. https://doi.org/10.3390/genes12111746","ista":"Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.","ama":"Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. 2021;12(11). doi:10.3390/genes12111746","chicago":"Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” Genes. MDPI, 2021. https://doi.org/10.3390/genes12111746.","short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021).","mla":"Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” Genes, vol. 12, no. 11, 1746, MDPI, 2021, doi:10.3390/genes12111746."},"article_type":"original","date_published":"2021-10-30T00:00:00Z","scopus_import":"1","day":"30","article_processing_charge":"No","has_accepted_license":"1","_id":"10281","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"status":"public","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","intvolume":" 12","oa_version":"Published Version","file":[{"file_size":1335308,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2021_Genes_Vasic.pdf","checksum":"256cb832a9c3051c7dc741f6423b8cbd","success":1,"date_updated":"2022-05-16T07:02:27Z","date_created":"2022-05-16T07:02:27Z","relation":"main_file","file_id":"11380"}],"type":"journal_article","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"abstract":[{"text":"Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems","lang":"eng"}],"issue":"11","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000834044200002"]},"quality_controlled":"1","isi":1,"project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"}],"doi":"10.3390/genes12111746","language":[{"iso":"eng"}],"month":"10","publication_identifier":{"eissn":["2073-4425"]},"year":"2021","acknowledgement":"This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811); Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was also supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24) both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes for her support in preparing this manuscript.","publication_status":"published","publisher":"MDPI","department":[{"_id":"GaNo"}],"author":[{"last_name":"Vasic","first_name":"Verica","full_name":"Vasic, Verica"},{"first_name":"Mattson S.O.","last_name":"Jones","full_name":"Jones, Mattson S.O."},{"id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","last_name":"Haslinger","first_name":"Denise","full_name":"Haslinger, Denise"},{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schmeisser","first_name":"Michael J.","full_name":"Schmeisser, Michael J."},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"last_name":"Chiocchetti","first_name":"Andreas G.","full_name":"Chiocchetti, Andreas G."}],"date_created":"2021-11-14T23:01:24Z","date_updated":"2023-08-14T11:46:12Z","volume":12,"article_number":"1746","file_date_updated":"2022-05-16T07:02:27Z","ec_funded":1},{"acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","year":"2021","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"GaNo"}],"author":[{"first_name":"María J","last_name":"Conde-Dusman","full_name":"Conde-Dusman, María J"},{"last_name":"Dey","first_name":"Partha N","full_name":"Dey, Partha N"},{"full_name":"Elía-Zudaire, Óscar","last_name":"Elía-Zudaire","first_name":"Óscar"},{"last_name":"Garcia Rabaneda","first_name":"Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","full_name":"Garcia Rabaneda, Luis E"},{"last_name":"García-Lira","first_name":"Carmen","full_name":"García-Lira, Carmen"},{"last_name":"Grand","first_name":"Teddy","full_name":"Grand, Teddy"},{"first_name":"Victor","last_name":"Briz","full_name":"Briz, Victor"},{"first_name":"Eric R","last_name":"Velasco","full_name":"Velasco, Eric R"},{"first_name":"Raül","last_name":"Andero Galí","full_name":"Andero Galí, Raül"},{"first_name":"Sergio","last_name":"Niñerola","full_name":"Niñerola, Sergio"},{"full_name":"Barco, Angel","last_name":"Barco","first_name":"Angel"},{"last_name":"Paoletti","first_name":"Pierre","full_name":"Paoletti, Pierre"},{"full_name":"Wesseling, John F","last_name":"Wesseling","first_name":"John F"},{"full_name":"Gardoni, Fabrizio","first_name":"Fabrizio","last_name":"Gardoni"},{"full_name":"Tavalin, Steven J","last_name":"Tavalin","first_name":"Steven J"},{"first_name":"Isabel","last_name":"Perez-Otaño","full_name":"Perez-Otaño, Isabel"}],"date_updated":"2023-08-14T11:50:50Z","date_created":"2021-11-18T06:59:45Z","volume":10,"article_number":"e71575","file_date_updated":"2021-11-18T07:02:02Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000720945900001"]},"quality_controlled":"1","isi":1,"doi":"10.7554/elife.71575","language":[{"iso":"eng"}],"month":"11","publication_identifier":{"issn":["2050-084X"]},"_id":"10301","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","status":"public","ddc":["570"],"intvolume":" 10","file":[{"file_id":"10302","relation":"main_file","success":1,"checksum":"59318e9e41507cec83c2f4070e6ad540","date_created":"2021-11-18T07:02:02Z","date_updated":"2021-11-18T07:02:02Z","access_level":"open_access","file_name":"elife-71575-v1.pdf","creator":"lgarciar","content_type":"application/pdf","file_size":2477302}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"publication":"eLife","citation":{"apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575","ieee":"M. J. Conde-Dusman et al., “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife, vol. 10. eLife Sciences Publications, 2021.","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 2021;10. doi:10.7554/elife.71575","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).","mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife, vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575."},"article_type":"original","date_published":"2021-11-17T00:00:00Z","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"day":"17","has_accepted_license":"1","article_processing_charge":"No"},{"pmid":1,"year":"2021","acknowledgement":"We acknowledge that Université Laval stands on the traditional and unceded land of the Huron-Wendat peoples; and that the University of Victoria exists on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ peoples have relationships to this land. We thank Emmanuel Planel for the access to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank the Centre for Advanced Materials and Related Technology for the access to the confocal microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from Fondation Famille-Choquette. K.B. was supported by excellence scholarships from Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S. were supported by postdoctoral fellowships from FRQS. This study was funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T. and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B, by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition.","publisher":"Elsevier","department":[{"_id":"GaNo"}],"publication_status":"published","author":[{"last_name":"Picard","first_name":"Katherine","full_name":"Picard, Katherine"},{"full_name":"Bisht, Kanchan","last_name":"Bisht","first_name":"Kanchan"},{"first_name":"Silvia","last_name":"Poggini","full_name":"Poggini, Silvia"},{"last_name":"Garofalo","first_name":"Stefano","full_name":"Garofalo, Stefano"},{"last_name":"Golia","first_name":"Maria Teresa","full_name":"Golia, Maria Teresa"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette"},{"full_name":"Abdallah, Fatima","first_name":"Fatima","last_name":"Abdallah"},{"full_name":"Ciano Albanese, Naomi","first_name":"Naomi","last_name":"Ciano Albanese"},{"first_name":"Irmgard","last_name":"Amrein","full_name":"Amrein, Irmgard"},{"first_name":"Nathalie","last_name":"Vernoux","full_name":"Vernoux, Nathalie"},{"full_name":"Sharma, Kaushik","last_name":"Sharma","first_name":"Kaushik"},{"last_name":"Hui","first_name":"Chin Wai","full_name":"Hui, Chin Wai"},{"last_name":"C. Savage","first_name":"Julie","full_name":"C. Savage, Julie"},{"full_name":"Limatola, Cristina","first_name":"Cristina","last_name":"Limatola"},{"last_name":"Ragozzino","first_name":"Davide","full_name":"Ragozzino, Davide"},{"last_name":"Maggi","first_name":"Laura","full_name":"Maggi, Laura"},{"first_name":"Igor","last_name":"Branchi","full_name":"Branchi, Igor"},{"first_name":"Marie Ève","last_name":"Tremblay","full_name":"Tremblay, Marie Ève"}],"volume":97,"date_created":"2021-08-22T22:01:21Z","date_updated":"2023-10-03T09:49:18Z","publication_identifier":{"issn":["0889-1591"]},"month":"10","main_file_link":[{"url":"https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf","open_access":"1"}],"external_id":{"isi":["000702878400007"],"pmid":["34343616"]},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.1016/j.bbi.2021.07.022","language":[{"iso":"eng"}],"type":"journal_article","abstract":[{"text":"Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress.","lang":"eng"}],"_id":"9953","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 97","title":"Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice","status":"public","oa_version":"Submitted Version","scopus_import":"1","article_processing_charge":"No","day":"01","citation":{"chicago":"Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity. Elsevier, 2021. https://doi.org/10.1016/j.bbi.2021.07.022.","mla":"Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity, vol. 97, Elsevier, 2021, pp. 423–39, doi:10.1016/j.bbi.2021.07.022.","short":"K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F. Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C. Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain, Behavior, and Immunity 97 (2021) 423–439.","ista":"Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F, Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 97, 423–439.","ieee":"K. Picard et al., “Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice,” Brain, Behavior, and Immunity, vol. 97. Elsevier, pp. 423–439, 2021.","apa":"Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B., … Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. Elsevier. https://doi.org/10.1016/j.bbi.2021.07.022","ama":"Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 2021;97:423-439. doi:10.1016/j.bbi.2021.07.022"},"publication":"Brain, Behavior, and Immunity","page":"423-439","article_type":"original","date_published":"2021-10-01T00:00:00Z"},{"date_created":"2020-11-06T08:39:01Z","date_updated":"2023-10-18T06:45:30Z","volume":41,"author":[{"full_name":"Tournier, N","last_name":"Tournier","first_name":"N"},{"full_name":"Goutal, S","last_name":"Goutal","first_name":"S"},{"first_name":"S","last_name":"Mairinger","full_name":"Mairinger, S"},{"full_name":"Lozano, IH","last_name":"Lozano","first_name":"IH"},{"last_name":"Filip","first_name":"T","full_name":"Filip, T"},{"last_name":"Sauberer","first_name":"M","full_name":"Sauberer, M"},{"full_name":"Caillé, F","first_name":"F","last_name":"Caillé"},{"full_name":"Breuil, L","last_name":"Breuil","first_name":"L"},{"first_name":"J","last_name":"Stanek","full_name":"Stanek, J"},{"last_name":"Freeman","first_name":"AF","full_name":"Freeman, AF"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"full_name":"Truillet, C","last_name":"Truillet","first_name":"C"},{"full_name":"Wanek, T","first_name":"T","last_name":"Wanek"},{"full_name":"Langer, O","last_name":"Langer","first_name":"O"}],"publication_status":"published","publisher":"SAGE Publications","department":[{"_id":"GaNo"}],"year":"2021","pmid":1,"language":[{"iso":"eng"}],"doi":"10.1177/0271678X20965500","quality_controlled":"1","isi":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/","open_access":"1"}],"oa":1,"external_id":{"pmid":["33081568"],"isi":["000664214100012"]},"month":"07","publication_identifier":{"issn":["0271-678x"],"eissn":["1559-7016"]},"oa_version":"Published Version","title":"Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib","status":"public","intvolume":" 41","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8730","abstract":[{"lang":"eng","text":"P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors."}],"issue":"7","type":"journal_article","date_published":"2021-07-01T00:00:00Z","article_type":"original","page":"1634-1646","publication":"Journal of Cerebral Blood Flow and Metabolism","citation":{"ama":"Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 2021;41(7):1634-1646. doi:10.1177/0271678X20965500","ieee":"N. Tournier et al., “Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” Journal of Cerebral Blood Flow and Metabolism, vol. 41, no. 7. SAGE Publications, pp. 1634–1646, 2021.","apa":"Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M., … Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. SAGE Publications. https://doi.org/10.1177/0271678X20965500","ista":"Tournier N, Goutal S, Mairinger S, Lozano I, Filip T, Sauberer M, Caillé F, Breuil L, Stanek J, Freeman A, Novarino G, Truillet C, Wanek T, Langer O. 2021. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 41(7), 1634–1646.","short":"N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F. Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek, O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646.","mla":"Tournier, N., et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Journal of Cerebral Blood Flow and Metabolism, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46, doi:10.1177/0271678X20965500.","chicago":"Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé, et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Journal of Cerebral Blood Flow and Metabolism. SAGE Publications, 2021. https://doi.org/10.1177/0271678X20965500."},"day":"01","article_processing_charge":"No","scopus_import":"1"}]