[{"type":"journal_article","abstract":[{"text":"SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder.","lang":"eng"}],"issue":"12","title":"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition","status":"public","ddc":["570"],"intvolume":" 21","_id":"3","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Submitted Version","file":[{"file_size":8167169,"content_type":"application/pdf","creator":"dernst","file_name":"2017_NatureNeuroscience_Deliu.pdf","access_level":"open_access","date_updated":"2020-07-14T12:45:58Z","date_created":"2019-04-09T07:41:57Z","checksum":"60abd0f05b7cdc08a6b0ec460884084f","relation":"main_file","file_id":"6255"}],"pubrep_id":"1071","scopus_import":"1","day":"19","has_accepted_license":"1","article_processing_charge":"No","article_type":"original","page":"1717 - 1727","publication":"Nature Neuroscience","citation":{"mla":"Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.","short":"E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727.","chicago":"Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2.","ama":"Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2","ista":"Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727.","ieee":"E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.","apa":"Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2"},"date_published":"2018-11-19T00:00:00Z","file_date_updated":"2020-07-14T12:45:58Z","publist_id":"8054","publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"GaNo"},{"_id":"EdHa"}],"acknowledgement":"This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.","year":"2018","date_created":"2018-12-11T11:44:05Z","date_updated":"2024-03-28T23:30:45Z","volume":21,"author":[{"full_name":"Deliu, Elena","last_name":"Deliu","first_name":"Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Arecco, Niccoló","last_name":"Arecco","first_name":"Niccoló"},{"first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096"},{"first_name":"Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena"},{"last_name":"Girardot","first_name":"Charles","full_name":"Girardot, Charles"},{"full_name":"Käsper, Eva","first_name":"Eva","last_name":"Käsper"},{"full_name":"Kozlova, Alena","id":"C50A9596-02D0-11E9-976E-E38CFE5CBC1D","first_name":"Alena","last_name":"Kozlova"},{"full_name":"Kishi, Kasumi","last_name":"Kishi","first_name":"Kasumi","id":"3065DFC4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Chiaradia, Ilaria","id":"B6467F20-02D0-11E9-BDA5-E960C241894A","orcid":"0000-0002-9529-4464","first_name":"Ilaria","last_name":"Chiaradia"},{"full_name":"Noh, Kyung","first_name":"Kyung","last_name":"Noh"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/","description":"News on IST Homepage","relation":"press_release"}],"record":[{"relation":"popular_science","status":"public","id":"6074"},{"id":"12364","status":"public","relation":"dissertation_contains"}]},"month":"11","quality_controlled":"1","isi":1,"project":[{"name":"Probing development and reversibility of autism spectrum disorders","_id":"254BA948-B435-11E9-9278-68D0E5697425","grant_number":"401299"}],"external_id":{"isi":["000451324700010"]},"oa":1,"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41593-018-0266-2"},{"type":"journal_article","publist_id":"7290","abstract":[{"lang":"eng","text":"The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological processes. Although some sympathetic stimulatory effects of this system have been reported, its central cardiovascular regulatory properties are poorly characterized. VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces inositol 1,4,5-trisphosphate receptor-mediated Ca2+ mobilization, membrane depolarization and activation of P/Q-type Ca2+ channels. In vivo, this pathway converges onto transient reduction in heart rate of conscious rats. Therefore we demonstrate a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart rate, adding to the complexity of PACAP-mediated cardiovascular modulation."}],"extern":1,"_id":"529","year":"2017","acknowledgement":"This study was supported by startup funds from the Jefferson College of Pharmacy, and by the National Institutes of Health DA023204 (to M.E.A) and P30 DA 013429 to Center for Substance Abuse Research, Temple University.","intvolume":" 1657","publisher":"Elsevier","title":"Effects of VPAC1 activation in nucleus ambiguus neurons","publication_status":"published","status":"public","author":[{"full_name":"Gherghina, Florin L","first_name":"Florin","last_name":"Gherghina"},{"first_name":"Andrei","last_name":"Tica","full_name":"Tica, Andrei A"},{"full_name":"Elena Deliu","first_name":"Elena","last_name":"Deliu","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5293"},{"last_name":"Abood","first_name":"Mary","full_name":"Abood, Mary E"},{"first_name":"G.","last_name":"Brailoiu","full_name":"Brailoiu, G. Christina"},{"full_name":"Brǎiloiu, Eugen","first_name":"Eugen","last_name":"Brǎiloiu"}],"volume":1657,"date_created":"2018-12-11T11:46:59Z","date_updated":"2021-01-12T08:01:26Z","month":"02","day":"15","citation":{"chicago":"Gherghina, Florin, Andrei Tica, Elena Deliu, Mary Abood, G. Brailoiu, and Eugen Brǎiloiu. “Effects of VPAC1 Activation in Nucleus Ambiguus Neurons.” Brain Research. Elsevier, 2017. https://doi.org/10.1016/j.brainres.2016.12.026.","short":"F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, E. Brǎiloiu, Brain Research 1657 (2017) 297–303.","mla":"Gherghina, Florin, et al. “Effects of VPAC1 Activation in Nucleus Ambiguus Neurons.” Brain Research, vol. 1657, Elsevier, 2017, pp. 297–303, doi:10.1016/j.brainres.2016.12.026.","apa":"Gherghina, F., Tica, A., Deliu, E., Abood, M., Brailoiu, G., & Brǎiloiu, E. (2017). Effects of VPAC1 activation in nucleus ambiguus neurons. Brain Research. Elsevier. https://doi.org/10.1016/j.brainres.2016.12.026","ieee":"F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, and E. Brǎiloiu, “Effects of VPAC1 activation in nucleus ambiguus neurons,” Brain Research, vol. 1657. Elsevier, pp. 297–303, 2017.","ista":"Gherghina F, Tica A, Deliu E, Abood M, Brailoiu G, Brǎiloiu E. 2017. Effects of VPAC1 activation in nucleus ambiguus neurons. Brain Research. 1657, 297–303.","ama":"Gherghina F, Tica A, Deliu E, Abood M, Brailoiu G, Brǎiloiu E. Effects of VPAC1 activation in nucleus ambiguus neurons. Brain Research. 2017;1657:297-303. doi:10.1016/j.brainres.2016.12.026"},"publication":"Brain Research","page":"297 - 303","quality_controlled":0,"doi":"10.1016/j.brainres.2016.12.026","date_published":"2017-02-15T00:00:00Z"},{"status":"public","title":"Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder","intvolume":" 224","_id":"634","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"None","alternative_title":["ADVSANAT"],"type":"book_chapter","abstract":[{"text":"As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans.","lang":"eng"}],"page":"189 - 211","publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","citation":{"ista":"Schroeder J, Deliu E, Novarino G, Schmeisser M. 2017.Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In: Translational Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 189–211.","apa":"Schroeder, J., Deliu, E., Novarino, G., & Schmeisser, M. (2017). Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 189–211). Springer. https://doi.org/10.1007/978-3-319-52498-6_10","ieee":"J. Schroeder, E. Deliu, G. Novarino, and M. Schmeisser, “Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder,” in Translational Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser and T. Boekers, Eds. Springer, 2017, pp. 189–211.","ama":"Schroeder J, Deliu E, Novarino G, Schmeisser M. Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In: Schmeisser M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer; 2017:189-211. doi:10.1007/978-3-319-52498-6_10","chicago":"Schroeder, Jan, Elena Deliu, Gaia Novarino, and Michael Schmeisser. “Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, 224:189–211. Advances in Anatomy Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_10.","mla":"Schroeder, Jan, et al. “Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.” Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, vol. 224, Springer, 2017, pp. 189–211, doi:10.1007/978-3-319-52498-6_10.","short":"J. Schroeder, E. Deliu, G. Novarino, M. Schmeisser, in:, M. Schmeisser, T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder, Springer, 2017, pp. 189–211."},"date_published":"2017-05-28T00:00:00Z","series_title":"Advances in Anatomy Embryology and Cell Biology","scopus_import":1,"day":"28","publication_status":"published","publisher":"Springer","editor":[{"full_name":"Schmeisser, Michael","last_name":"Schmeisser","first_name":"Michael"},{"full_name":"Boekers, Tobias","first_name":"Tobias","last_name":"Boekers"}],"department":[{"_id":"GaNo"}],"year":"2017","date_created":"2018-12-11T11:47:37Z","date_updated":"2021-01-12T08:07:08Z","volume":224,"author":[{"full_name":"Schroeder, Jan","first_name":"Jan","last_name":"Schroeder"},{"full_name":"Deliu, Elena","first_name":"Elena","last_name":"Deliu","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5293"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"full_name":"Schmeisser, Michael","last_name":"Schmeisser","first_name":"Michael"}],"publist_id":"7156","quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Transmembrane Transporters in Health and Disease","_id":"25473368-B435-11E9-9278-68D0E5697425","grant_number":"F03523"}],"language":[{"iso":"eng"}],"doi":"10.1007/978-3-319-52498-6_10","month":"05","publication_identifier":{"eisbn":["978-3-319-52498-6"]}},{"oa_version":"Submitted Version","intvolume":" 178","status":"public","title":"HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"714","abstract":[{"lang":"eng","text":"Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients."}],"type":"journal_article","date_published":"2017-09-01T00:00:00Z","page":"7 - 14","article_type":"original","citation":{"mla":"Brailoiu, Gabriela, et al. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence, vol. 178, Elsevier, 2017, pp. 7–14, doi:10.1016/j.drugalcdep.2017.04.015.","short":"G. Brailoiu, E. Deliu, J. Barr, L. Console Bram, A. Ciuciu, M. Abood, E. Unterwald, E. Brǎiloiu, Drug and Alcohol Dependence 178 (2017) 7–14.","chicago":"Brailoiu, Gabriela, Elena Deliu, Jeffrey Barr, Linda Console Bram, Alexandra Ciuciu, Mary Abood, Ellen Unterwald, and Eugen Brǎiloiu. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence. Elsevier, 2017. https://doi.org/10.1016/j.drugalcdep.2017.04.015.","ama":"Brailoiu G, Deliu E, Barr J, et al. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 2017;178:7-14. doi:10.1016/j.drugalcdep.2017.04.015","ista":"Brailoiu G, Deliu E, Barr J, Console Bram L, Ciuciu A, Abood M, Unterwald E, Brǎiloiu E. 2017. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 178, 7–14.","ieee":"G. Brailoiu et al., “HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens,” Drug and Alcohol Dependence, vol. 178. Elsevier, pp. 7–14, 2017.","apa":"Brailoiu, G., Deliu, E., Barr, J., Console Bram, L., Ciuciu, A., Abood, M., … Brǎiloiu, E. (2017). HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. Elsevier. https://doi.org/10.1016/j.drugalcdep.2017.04.015"},"publication":"Drug and Alcohol Dependence","article_processing_charge":"No","day":"01","scopus_import":1,"volume":178,"date_updated":"2021-01-12T08:12:00Z","date_created":"2018-12-11T11:48:05Z","author":[{"last_name":"Brailoiu","first_name":"Gabriela","full_name":"Brailoiu, Gabriela"},{"id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5293","first_name":"Elena","last_name":"Deliu","full_name":"Deliu, Elena"},{"full_name":"Barr, Jeffrey","last_name":"Barr","first_name":"Jeffrey"},{"last_name":"Console Bram","first_name":"Linda","full_name":"Console Bram, Linda"},{"last_name":"Ciuciu","first_name":"Alexandra","full_name":"Ciuciu, Alexandra"},{"last_name":"Abood","first_name":"Mary","full_name":"Abood, Mary"},{"full_name":"Unterwald, Ellen","first_name":"Ellen","last_name":"Unterwald"},{"full_name":"Brǎiloiu, Eugen","first_name":"Eugen","last_name":"Brǎiloiu"}],"publisher":"Elsevier","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"year":"2017","acknowledgement":"This work was supported by the National Institutes of Health grants DA035926 (to MEA), and P30DA013429 (to EMU).","publist_id":"6967","language":[{"iso":"eng"}],"doi":"10.1016/j.drugalcdep.2017.04.015","quality_controlled":"1","oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797705","open_access":"1"}],"external_id":{"pmid":["28623807"]},"publication_identifier":{"issn":["03768716"]},"month":"09"},{"date_published":"2017-12-04T00:00:00Z","article_type":"original","page":"23 - 32","publication":"Neuroscience","citation":{"ieee":"E. Brǎiloiu et al., “Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus,” Neuroscience, vol. 365. Elsevier, pp. 23–32, 2017.","apa":"Brǎiloiu, E., Mcguire, M., Shuler, S., Deliu, E., Barr, J., Abood, M., & Brailoiu, G. (2017). Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2017.09.034","ista":"Brǎiloiu E, Mcguire M, Shuler S, Deliu E, Barr J, Abood M, Brailoiu G. 2017. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 365, 23–32.","ama":"Brǎiloiu E, Mcguire M, Shuler S, et al. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 2017;365:23-32. doi:10.1016/j.neuroscience.2017.09.034","chicago":"Brǎiloiu, Eugen, Matthew Mcguire, Shadaria Shuler, Elena Deliu, Jeffrey Barr, Mary Abood, and Gabriela Brailoiu. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience. Elsevier, 2017. https://doi.org/10.1016/j.neuroscience.2017.09.034.","short":"E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu, Neuroscience 365 (2017) 23–32.","mla":"Brǎiloiu, Eugen, et al. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience, vol. 365, Elsevier, 2017, pp. 23–32, doi:10.1016/j.neuroscience.2017.09.034."},"day":"04","article_processing_charge":"No","scopus_import":"1","oa_version":"Submitted Version","title":"Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus","status":"public","intvolume":" 365","_id":"747","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","abstract":[{"text":"Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia.","lang":"eng"}],"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.neuroscience.2017.09.034","isi":1,"quality_controlled":"1","external_id":{"pmid":["28951324"],"isi":["000415966200003"]},"oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458","open_access":"1"}],"month":"12","publication_identifier":{"issn":["03064522"]},"date_updated":"2023-09-27T12:26:59Z","date_created":"2018-12-11T11:48:17Z","volume":365,"author":[{"last_name":"Brǎiloiu","first_name":"Eugen","full_name":"Brǎiloiu, Eugen"},{"full_name":"Mcguire, Matthew","first_name":"Matthew","last_name":"Mcguire"},{"full_name":"Shuler, Shadaria","first_name":"Shadaria","last_name":"Shuler"},{"full_name":"Deliu, Elena","last_name":"Deliu","first_name":"Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Barr, Jeffrey","last_name":"Barr","first_name":"Jeffrey"},{"full_name":"Abood, Mary","first_name":"Mary","last_name":"Abood"},{"full_name":"Brailoiu, Gabriela","last_name":"Brailoiu","first_name":"Gabriela"}],"publication_status":"published","publisher":"Elsevier","department":[{"_id":"GaNo"}],"year":"2017","pmid":1,"publist_id":"6911"},{"doi":"10.1016/j.cell.2016.11.013","language":[{"iso":"eng"}],"oa":1,"quality_controlled":"1","project":[{"grant_number":"F03523","_id":"25473368-B435-11E9-9278-68D0E5697425","name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF"}],"month":"12","author":[{"full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu","first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Deliu","first_name":"Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","full_name":"Deliu, Elena"},{"full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","first_name":"Christoph","last_name":"Dotter"},{"last_name":"Kara","first_name":"Majdi","full_name":"Kara, Majdi"},{"first_name":"Philipp","last_name":"Janiesch","full_name":"Janiesch, Philipp"},{"full_name":"Scalise, Mariafrancesca","first_name":"Mariafrancesca","last_name":"Scalise"},{"full_name":"Galluccio, Michele","last_name":"Galluccio","first_name":"Michele"},{"first_name":"Mateja","last_name":"Tesulov","full_name":"Tesulov, Mateja"},{"full_name":"Morelli, Emanuela","last_name":"Morelli","first_name":"Emanuela","id":"3F4D1282-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Fatma","last_name":"Sönmez","full_name":"Sönmez, Fatma"},{"last_name":"Bilgüvar","first_name":"Kaya","full_name":"Bilgüvar, Kaya"},{"first_name":"Ryuichi","last_name":"Ohgaki","full_name":"Ohgaki, Ryuichi"},{"full_name":"Kanai, Yoshikatsu","last_name":"Kanai","first_name":"Yoshikatsu"},{"full_name":"Johansen, Anide","first_name":"Anide","last_name":"Johansen"},{"full_name":"Esharif, Seham","first_name":"Seham","last_name":"Esharif"},{"first_name":"Tawfeg","last_name":"Ben Omran","full_name":"Ben Omran, Tawfeg"},{"full_name":"Topcu, Meral","last_name":"Topcu","first_name":"Meral"},{"first_name":"Avner","last_name":"Schlessinger","full_name":"Schlessinger, Avner"},{"full_name":"Indiveri, Cesare","last_name":"Indiveri","first_name":"Cesare"},{"full_name":"Duncan, Kent","last_name":"Duncan","first_name":"Kent"},{"full_name":"Caglayan, Ahmet","first_name":"Ahmet","last_name":"Caglayan"},{"first_name":"Murat","last_name":"Günel","full_name":"Günel, Murat"},{"full_name":"Gleeson, Joseph","last_name":"Gleeson","first_name":"Joseph"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"395"}]},"date_updated":"2024-03-28T23:30:12Z","date_created":"2018-12-11T11:50:35Z","volume":167,"year":"2016","acknowledgement":"This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu, and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900 to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.), the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility","publication_status":"published","publisher":"Cell Press","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:44:37Z","publist_id":"6170","date_published":"2016-12-01T00:00:00Z","publication":"Cell","citation":{"ista":"Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.","ieee":"D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167, no. 6. Cell Press, pp. 1481–1494, 2016.","apa":"Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013","ama":"Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494. doi:10.1016/j.cell.2016.11.013","chicago":"Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013.","mla":"Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.","short":"D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494."},"article_type":"original","page":"1481 - 1494","day":"01","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","pubrep_id":"771","file":[{"file_id":"5030","relation":"main_file","checksum":"7fe01ab12a6610d3db421e0136db2f77","date_updated":"2020-07-14T12:44:37Z","date_created":"2018-12-12T10:13:44Z","access_level":"open_access","file_name":"IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf","creator":"system","content_type":"application/pdf","file_size":73907957}],"oa_version":"Submitted Version","_id":"1183","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","ddc":["576","616"],"status":"public","title":"Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder","intvolume":" 167","abstract":[{"text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.","lang":"eng"}],"issue":"6","type":"journal_article"}]