[{"day":"01","article_processing_charge":"No","keyword":["Neurology (clinical)"],"scopus_import":"1","date_published":"2022-08-01T00:00:00Z","article_type":"original","page":"2687-2703","publication":"Brain","citation":{"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","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","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.","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.","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.","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.","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."},"abstract":[{"lang":"eng","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."}],"issue":"8","type":"journal_article","oa_version":"Published Version","status":"public","title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","intvolume":" 145","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12174","month":"08","publication_identifier":{"issn":["0006-8950"],"eissn":["1460-2156"]},"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.1093/brain/awac145","quality_controlled":"1","isi":1,"project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/brain/awac145"}],"external_id":{"isi":["000807770000001"]},"oa":1,"ec_funded":1,"date_created":"2023-01-12T12:11:45Z","date_updated":"2023-08-04T09:13:08Z","volume":145,"author":[{"full_name":"Guerrini, Renzo","first_name":"Renzo","last_name":"Guerrini"},{"full_name":"Mei, Davide","first_name":"Davide","last_name":"Mei"},{"last_name":"Szigeti","first_name":"Margit Katalin","orcid":"0000-0001-9500-8758","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87","full_name":"Szigeti, Margit Katalin"},{"full_name":"Pepe, Sara","last_name":"Pepe","first_name":"Sara"},{"last_name":"Koenig","first_name":"Mary Kay","full_name":"Koenig, Mary Kay"},{"first_name":"Gretchen","last_name":"Von Allmen","full_name":"Von Allmen, Gretchen"},{"first_name":"Megan T","last_name":"Cho","full_name":"Cho, Megan T"},{"first_name":"Kimberly","last_name":"McDonald","full_name":"McDonald, Kimberly"},{"full_name":"Baker, Janice","last_name":"Baker","first_name":"Janice"},{"full_name":"Bhambhani, Vikas","last_name":"Bhambhani","first_name":"Vikas"},{"last_name":"Powis","first_name":"Zöe","full_name":"Powis, Zöe"},{"first_name":"Lance","last_name":"Rodan","full_name":"Rodan, Lance"},{"last_name":"Nabbout","first_name":"Rima","full_name":"Nabbout, Rima"},{"full_name":"Barcia, Giulia","first_name":"Giulia","last_name":"Barcia"},{"full_name":"Rosenfeld, Jill A","last_name":"Rosenfeld","first_name":"Jill A"},{"first_name":"Carlos A","last_name":"Bacino","full_name":"Bacino, Carlos A"},{"full_name":"Mignot, Cyril","first_name":"Cyril","last_name":"Mignot"},{"full_name":"Power, Lillian H","first_name":"Lillian H","last_name":"Power"},{"full_name":"Harris, Catharine J","last_name":"Harris","first_name":"Catharine J"},{"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"},{"first_name":"Riikka","last_name":"Keski Filppula","full_name":"Keski Filppula, Riikka"},{"full_name":"Vieira, Päivi","last_name":"Vieira","first_name":"Päivi"},{"full_name":"Hildebrandt, Clara","first_name":"Clara","last_name":"Hildebrandt"},{"last_name":"Sacharow","first_name":"Stephanie","full_name":"Sacharow, Stephanie"},{"full_name":"Maragliano, Luca","last_name":"Maragliano","first_name":"Luca"},{"last_name":"Benfenati","first_name":"Fabio","full_name":"Benfenati, 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","first_name":"Florence","last_name":"Petit"},{"last_name":"de Sainte Agathe","first_name":"Jean Madeleine","full_name":"de Sainte Agathe, Jean Madeleine"},{"first_name":"Barbara","last_name":"Hallinan","full_name":"Hallinan, Barbara"},{"first_name":"Yue","last_name":"Si","full_name":"Si, Yue"},{"last_name":"Wentzensen","first_name":"Ingrid M","full_name":"Wentzensen, Ingrid M"},{"first_name":"Fanggeng","last_name":"Zou","full_name":"Zou, Fanggeng"},{"full_name":"Narayanan, Vinodh","first_name":"Vinodh","last_name":"Narayanan"},{"first_name":"Naomichi","last_name":"Matsumoto","full_name":"Matsumoto, Naomichi"},{"first_name":"Alessandra","last_name":"Boncristiano","full_name":"Boncristiano, Alessandra"},{"full_name":"la Marca, Giancarlo","last_name":"la Marca","first_name":"Giancarlo"},{"full_name":"Kato, Mitsuhiro","last_name":"Kato","first_name":"Mitsuhiro"},{"first_name":"Kristin","last_name":"Anderson","full_name":"Anderson, Kristin"},{"full_name":"Barba, Carmen","first_name":"Carmen","last_name":"Barba"},{"last_name":"Sturiale","first_name":"Luisa","full_name":"Sturiale, Luisa"},{"last_name":"Garozzo","first_name":"Domenico","full_name":"Garozzo, Domenico"},{"full_name":"Bei, Roberto","first_name":"Roberto","last_name":"Bei"},{"full_name":"Masuelli, Laura","last_name":"Masuelli","first_name":"Laura"},{"full_name":"Conti, Valerio","first_name":"Valerio","last_name":"Conti"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"full_name":"Fassio, Anna","last_name":"Fassio","first_name":"Anna"}],"publication_status":"published","publisher":"Oxford University Press","department":[{"_id":"GaNo"}],"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"},{"language":[{"iso":"eng"}],"doi":"10.3389/fonc.2022.983507","quality_controlled":"1","isi":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":{"pmid":["36091138"],"isi":["000856524900001"]},"month":"08","publication_identifier":{"issn":["2234-943X"]},"date_updated":"2023-08-04T09:54:16Z","date_created":"2023-01-16T10:00:28Z","volume":12,"author":[{"last_name":"Basilico","first_name":"Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette"},{"first_name":"Ilaria Elena","last_name":"Palamà","full_name":"Palamà, Ilaria Elena"},{"last_name":"D’Amone","first_name":"Stefania","full_name":"D’Amone, Stefania"},{"first_name":"Clotilde","last_name":"Lauro","full_name":"Lauro, Clotilde"},{"full_name":"Rosito, Maria","last_name":"Rosito","first_name":"Maria"},{"full_name":"Grieco, Maddalena","first_name":"Maddalena","last_name":"Grieco"},{"first_name":"Patrizia","last_name":"Ratano","full_name":"Ratano, Patrizia"},{"last_name":"Cordella","first_name":"Federica","full_name":"Cordella, Federica"},{"first_name":"Caterina","last_name":"Sanchini","full_name":"Sanchini, Caterina"},{"last_name":"Di Angelantonio","first_name":"Silvia","full_name":"Di Angelantonio, Silvia"},{"last_name":"Ragozzino","first_name":"Davide","full_name":"Ragozzino, Davide"},{"full_name":"Cascione, Mariafrancesca","last_name":"Cascione","first_name":"Mariafrancesca"},{"full_name":"Gigli, Giuseppe","first_name":"Giuseppe","last_name":"Gigli"},{"first_name":"Barbara","last_name":"Cortese","full_name":"Cortese, Barbara"}],"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Frontiers Media","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.","pmid":1,"license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2023-01-30T10:25:21Z","article_number":"983507","date_published":"2022-08-25T00:00:00Z","article_type":"original","publication":"Frontiers in Oncology","citation":{"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).","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.","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.","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","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","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."},"day":"25","article_processing_charge":"No","has_accepted_license":"1","keyword":["Cancer Research","Oncology"],"scopus_import":"1","oa_version":"Published Version","file":[{"file_id":"12450","relation":"main_file","success":1,"checksum":"efc7edf9f626af31853790c5b598a68c","date_created":"2023-01-30T10:25:21Z","date_updated":"2023-01-30T10:25:21Z","access_level":"open_access","file_name":"2022_FrontiersOntology_Basilico.pdf","creator":"dernst","file_size":13588502,"content_type":"application/pdf"}],"ddc":["570"],"status":"public","title":"Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells","intvolume":" 12","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12268","abstract":[{"lang":"eng","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."}],"type":"journal_article"},{"type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"1","title":"Microglia control glutamatergic synapses in the adult mouse hippocampus","status":"public","ddc":["570"],"intvolume":" 70","_id":"10818","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"file_name":"2021_Glia_Basilico.pdf","access_level":"open_access","file_size":5340294,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"10819","date_updated":"2022-03-04T08:55:27Z","date_created":"2022-03-04T08:55:27Z","checksum":"f10a897290e66c0a062e04ba91db6c17","success":1}],"oa_version":"Published Version","keyword":["Cellular and Molecular Neuroscience","Neurology"],"scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1","article_type":"original","page":"173-195","publication":"Glia","citation":{"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","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.","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","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.","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.","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."},"date_published":"2022-01-01T00:00:00Z","license":"https://creativecommons.org/licenses/by-nc/4.0/","file_date_updated":"2022-03-04T08:55:27Z","publication_status":"published","publisher":"Wiley","department":[{"_id":"GaNo"}],"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.","year":"2022","pmid":1,"date_created":"2022-03-04T08:53:37Z","date_updated":"2023-09-05T16:01:23Z","volume":70,"author":[{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","last_name":"Basilico","full_name":"Basilico, Bernadette"},{"last_name":"Ferrucci","first_name":"Laura","full_name":"Ferrucci, Laura"},{"full_name":"Ratano, Patrizia","last_name":"Ratano","first_name":"Patrizia"},{"first_name":"Maria T.","last_name":"Golia","full_name":"Golia, Maria T."},{"first_name":"Alfonso","last_name":"Grimaldi","full_name":"Grimaldi, Alfonso"},{"first_name":"Maria","last_name":"Rosito","full_name":"Rosito, Maria"},{"last_name":"Ferretti","first_name":"Valentina","full_name":"Ferretti, Valentina"},{"full_name":"Reverte, Ingrid","first_name":"Ingrid","last_name":"Reverte"},{"first_name":"Caterina","last_name":"Sanchini","full_name":"Sanchini, Caterina"},{"first_name":"Maria C.","last_name":"Marrone","full_name":"Marrone, Maria C."},{"first_name":"Maria","last_name":"Giubettini","full_name":"Giubettini, Maria"},{"last_name":"De Turris","first_name":"Valeria","full_name":"De Turris, Valeria"},{"last_name":"Salerno","first_name":"Debora","full_name":"Salerno, Debora"},{"last_name":"Garofalo","first_name":"Stefano","full_name":"Garofalo, Stefano"},{"first_name":"Marie‐Kim","last_name":"St‐Pierre","full_name":"St‐Pierre, Marie‐Kim"},{"full_name":"Carrier, Micael","last_name":"Carrier","first_name":"Micael"},{"last_name":"Renzi","first_name":"Massimiliano","full_name":"Renzi, Massimiliano"},{"first_name":"Francesca","last_name":"Pagani","full_name":"Pagani, Francesca"},{"last_name":"Modi","first_name":"Brijesh","full_name":"Modi, Brijesh"},{"full_name":"Raspa, Marcello","last_name":"Raspa","first_name":"Marcello"},{"full_name":"Scavizzi, Ferdinando","last_name":"Scavizzi","first_name":"Ferdinando"},{"first_name":"Cornelius T.","last_name":"Gross","full_name":"Gross, Cornelius T."},{"first_name":"Silvia","last_name":"Marinelli","full_name":"Marinelli, Silvia"},{"full_name":"Tremblay, Marie‐Ève","first_name":"Marie‐Ève","last_name":"Tremblay"},{"full_name":"Caprioli, Daniele","last_name":"Caprioli","first_name":"Daniele"},{"full_name":"Maggi, Laura","first_name":"Laura","last_name":"Maggi"},{"last_name":"Limatola","first_name":"Cristina","full_name":"Limatola, Cristina"},{"last_name":"Di Angelantonio","first_name":"Silvia","full_name":"Di Angelantonio, Silvia"},{"first_name":"Davide","last_name":"Ragozzino","full_name":"Ragozzino, Davide"}],"month":"01","publication_identifier":{"issn":["0894-1491"],"eissn":["1098-1136"]},"isi":1,"quality_controlled":"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)"},"oa":1,"external_id":{"pmid":["34661306"],"isi":["000708025800001"]},"language":[{"iso":"eng"}],"doi":"10.1002/glia.24101"},{"type":"preprint","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"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11943","year":"2022","status":"public","publication_status":"submitted","title":"Saturated reconstruction of living brain tissue","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","author":[{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"full_name":"Miguel Villalba, Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430","first_name":"Eder","last_name":"Miguel Villalba"},{"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"},{"full_name":"Lin, Zudi","last_name":"Lin","first_name":"Zudi"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"last_name":"Troidl","first_name":"Jakob","full_name":"Troidl, Jakob"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","last_name":"Jahr","full_name":"Jahr, Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"first_name":"Seth G. N.","last_name":"Grant","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"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Pfister, Hanspeter","first_name":"Hanspeter","last_name":"Pfister"},{"full_name":"Bickel, Bernd","last_name":"Bickel","first_name":"Bernd","orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-23T11:07:59Z","oa_version":"Preprint","day":"09","month":"05","article_processing_charge":"No","publication":"bioRxiv","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"citation":{"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.).","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.","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","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431"},"date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","language":[{"iso":"eng"}]},{"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_status":"submitted","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","status":"public","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11950","year":"2022","date_created":"2022-08-24T08:24:52Z","date_updated":"2024-03-28T23:30:20Z","oa_version":"Preprint","author":[{"full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","first_name":"Julia M","last_name":"Michalska"},{"full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","first_name":"Philipp"},{"full_name":"Korinkova, Hana","first_name":"Hana","last_name":"Korinkova","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"first_name":"Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","first_name":"Alessandro","last_name":"Venturino"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"full_name":"Jonas, Peter M","first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12470"}]},"month":"08","day":"18","article_processing_charge":"No","publication":"bioRxiv","main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"citation":{"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.).","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.","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","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."},"oa":1,"language":[{"iso":"eng"}],"date_published":"2022-08-18T00:00:00Z","doi":"10.1101/2022.08.17.504272"},{"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","pmid":1,"publication_status":"published","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"publisher":"Elsevier","author":[{"first_name":"Carlo Emanuele","last_name":"Villa","full_name":"Villa, Carlo Emanuele"},{"first_name":"Cristina","last_name":"Cheroni","full_name":"Cheroni, Cristina"},{"full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","first_name":"Christoph","last_name":"Dotter"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"last_name":"Oliveira","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","last_name":"Sacco","full_name":"Sacco, Roberto"},{"last_name":"Yahya","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ"},{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","first_name":"Jasmin"},{"last_name":"Gabriele","first_name":"Michele","full_name":"Gabriele, Michele"},{"full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik"},{"last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"full_name":"Gabitto, Mariano","first_name":"Mariano","last_name":"Gabitto"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"full_name":"Testa, Giuseppe","last_name":"Testa","first_name":"Giuseppe"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"id":"12364","relation":"dissertation_contains","status":"public"}]},"date_created":"2022-04-15T09:03:10Z","date_updated":"2024-03-28T23:30:45Z","volume":39,"article_number":"110615","file_date_updated":"2022-04-15T09:06:25Z","ec_funded":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":["35385734"],"isi":["000785983900003"]},"isi":1,"quality_controlled":"1","project":[{"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"},{"grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF"}],"doi":"10.1016/j.celrep.2022.110615","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"month":"04","publication_identifier":{"issn":["2211-1247"]},"_id":"11160","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","status":"public","ddc":["570"],"intvolume":" 39","file":[{"success":1,"checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_updated":"2022-04-15T09:06:25Z","date_created":"2022-04-15T09:06:25Z","file_id":"11164","relation":"main_file","creator":"dernst","file_size":"7808644","content_type":"application/pdf","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","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."}],"issue":"1","publication":"Cell Reports","citation":{"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.","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.","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.","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"},"article_type":"original","date_published":"2022-04-05T00:00:00Z","keyword":["General Biochemistry","Genetics and Molecular Biology"],"day":"05","article_processing_charge":"Yes","has_accepted_license":"1"},{"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"],"_id":"12364","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa_version":"Published Version","file":[{"date_updated":"2023-09-20T22:30:03Z","date_created":"2023-01-24T13:15:45Z","checksum":"896f4cac9adb6d3f26a6605772f4e1a3","file_id":"12365","embargo":"2023-09-19","relation":"main_file","creator":"cchlebak","content_type":"application/pdf","file_size":20457465,"file_name":"220923_Thesis_CDotter_Final.pdf","access_level":"open_access"},{"date_created":"2023-02-02T09:15:35Z","date_updated":"2023-09-20T22:30:03Z","checksum":"ad01bb20da163be6893b7af832e58419","relation":"source_file","file_id":"12482","file_size":22433512,"content_type":"application/x-zip-compressed","creator":"cchlebak","embargo_to":"open_access","file_name":"latex_source_CDotter_Thesis_2022.zip","access_level":"closed"}],"article_processing_charge":"No","has_accepted_license":"1","day":"19","page":"152","citation":{"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.","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.","ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094","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","ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria."},"date_published":"2022-09-19T00:00:00Z","ec_funded":1,"file_date_updated":"2023-09-20T22:30:03Z","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"publisher":"Institute of Science and Technology Austria","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"},{"id":"11160","relation":"part_of_dissertation","status":"public"}]},"author":[{"full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096"}],"publication_identifier":{"issn":["2663-337X"]},"month":"09","project":[{"grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425","name":"Probing development and reversibility of autism spectrum disorders"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","grant_number":"707964","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy"}],"oa":1,"language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"doi":"10.15479/at:ista:12094"},{"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.","publisher":"MDPI","department":[{"_id":"GaNo"}],"publication_status":"published","author":[{"last_name":"Vasic","first_name":"Verica","full_name":"Vasic, Verica"},{"full_name":"Jones, Mattson S.O.","first_name":"Mattson S.O.","last_name":"Jones"},{"last_name":"Haslinger","first_name":"Denise","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","full_name":"Haslinger, Denise"},{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schmeisser, Michael J.","first_name":"Michael J.","last_name":"Schmeisser"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Chiocchetti, Andreas G.","first_name":"Andreas G.","last_name":"Chiocchetti"}],"volume":12,"date_created":"2021-11-14T23:01:24Z","date_updated":"2023-08-14T11:46:12Z","article_number":"1746","ec_funded":1,"file_date_updated":"2022-05-16T07:02:27Z","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"]},"project":[{"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"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"}],"quality_controlled":"1","isi":1,"doi":"10.3390/genes12111746","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2073-4425"]},"month":"10","_id":"10281","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 12","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","status":"public","ddc":["570"],"oa_version":"Published Version","file":[{"file_name":"2021_Genes_Vasic.pdf","access_level":"open_access","content_type":"application/pdf","file_size":1335308,"creator":"dernst","relation":"main_file","file_id":"11380","date_created":"2022-05-16T07:02:27Z","date_updated":"2022-05-16T07:02:27Z","checksum":"256cb832a9c3051c7dc741f6423b8cbd","success":1}],"type":"journal_article","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"issue":"11","abstract":[{"lang":"eng","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"}],"citation":{"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","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.","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.","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."},"publication":"Genes","article_type":"original","date_published":"2021-10-30T00:00:00Z","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"30"},{"article_number":"e71575","file_date_updated":"2021-11-18T07:02:02Z","year":"2021","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).","publisher":"eLife Sciences Publications","department":[{"_id":"GaNo"}],"publication_status":"published","author":[{"full_name":"Conde-Dusman, María J","first_name":"María J","last_name":"Conde-Dusman"},{"full_name":"Dey, Partha N","last_name":"Dey","first_name":"Partha N"},{"full_name":"Elía-Zudaire, Óscar","last_name":"Elía-Zudaire","first_name":"Óscar"},{"id":"33D1B084-F248-11E8-B48F-1D18A9856A87","last_name":"Garcia Rabaneda","first_name":"Luis E","full_name":"Garcia Rabaneda, Luis E"},{"full_name":"García-Lira, Carmen","last_name":"García-Lira","first_name":"Carmen"},{"full_name":"Grand, Teddy","first_name":"Teddy","last_name":"Grand"},{"first_name":"Victor","last_name":"Briz","full_name":"Briz, Victor"},{"first_name":"Eric R","last_name":"Velasco","full_name":"Velasco, Eric R"},{"full_name":"Andero Galí, Raül","last_name":"Andero Galí","first_name":"Raül"},{"full_name":"Niñerola, Sergio","last_name":"Niñerola","first_name":"Sergio"},{"full_name":"Barco, Angel","first_name":"Angel","last_name":"Barco"},{"full_name":"Paoletti, Pierre","last_name":"Paoletti","first_name":"Pierre"},{"last_name":"Wesseling","first_name":"John F","full_name":"Wesseling, John F"},{"full_name":"Gardoni, Fabrizio","last_name":"Gardoni","first_name":"Fabrizio"},{"first_name":"Steven J","last_name":"Tavalin","full_name":"Tavalin, Steven J"},{"first_name":"Isabel","last_name":"Perez-Otaño","full_name":"Perez-Otaño, Isabel"}],"volume":10,"date_created":"2021-11-18T06:59:45Z","date_updated":"2023-08-14T11:50:50Z","publication_identifier":{"issn":["2050-084X"]},"month":"11","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"}],"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."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10301","intvolume":" 10","ddc":["570"],"status":"public","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","file":[{"creator":"lgarciar","content_type":"application/pdf","file_size":2477302,"access_level":"open_access","file_name":"elife-71575-v1.pdf","success":1,"checksum":"59318e9e41507cec83c2f4070e6ad540","date_created":"2021-11-18T07:02:02Z","date_updated":"2021-11-18T07:02:02Z","file_id":"10302","relation":"main_file"}],"oa_version":"Published Version","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"has_accepted_license":"1","article_processing_charge":"No","day":"17","citation":{"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","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.","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.","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","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.","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).","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."},"publication":"eLife","article_type":"original","date_published":"2021-11-17T00:00:00Z"},{"month":"10","publication_identifier":{"issn":["0889-1591"]},"isi":1,"quality_controlled":"1","main_file_link":[{"url":"https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf","open_access":"1"}],"external_id":{"pmid":["34343616"],"isi":["000702878400007"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1016/j.bbi.2021.07.022","publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Elsevier","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.","year":"2021","pmid":1,"date_created":"2021-08-22T22:01:21Z","date_updated":"2023-10-03T09:49:18Z","volume":97,"author":[{"first_name":"Katherine","last_name":"Picard","full_name":"Picard, Katherine"},{"full_name":"Bisht, Kanchan","first_name":"Kanchan","last_name":"Bisht"},{"full_name":"Poggini, Silvia","last_name":"Poggini","first_name":"Silvia"},{"last_name":"Garofalo","first_name":"Stefano","full_name":"Garofalo, Stefano"},{"first_name":"Maria Teresa","last_name":"Golia","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"},{"last_name":"Abdallah","first_name":"Fatima","full_name":"Abdallah, Fatima"},{"first_name":"Naomi","last_name":"Ciano Albanese","full_name":"Ciano Albanese, Naomi"},{"first_name":"Irmgard","last_name":"Amrein","full_name":"Amrein, Irmgard"},{"full_name":"Vernoux, Nathalie","first_name":"Nathalie","last_name":"Vernoux"},{"first_name":"Kaushik","last_name":"Sharma","full_name":"Sharma, Kaushik"},{"last_name":"Hui","first_name":"Chin Wai","full_name":"Hui, Chin Wai"},{"first_name":"Julie","last_name":"C. Savage","full_name":"C. Savage, Julie"},{"last_name":"Limatola","first_name":"Cristina","full_name":"Limatola, Cristina"},{"last_name":"Ragozzino","first_name":"Davide","full_name":"Ragozzino, Davide"},{"full_name":"Maggi, Laura","first_name":"Laura","last_name":"Maggi"},{"full_name":"Branchi, Igor","last_name":"Branchi","first_name":"Igor"},{"last_name":"Tremblay","first_name":"Marie Ève","full_name":"Tremblay, Marie Ève"}],"scopus_import":"1","day":"01","article_processing_charge":"No","article_type":"original","page":"423-439","publication":"Brain, Behavior, and Immunity","citation":{"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","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","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.","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.","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.","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."},"date_published":"2021-10-01T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","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."}],"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","intvolume":" 97","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"9953","oa_version":"Submitted Version"}]