--- _id: '3' abstract: - lang: eng 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. acknowledged_ssus: - _id: M-Shop - _id: PreCl 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. article_processing_charge: No article_type: original author: - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Niccoló full_name: Arecco, Niccoló last_name: Arecco - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Charles full_name: Girardot, Charles last_name: Girardot - first_name: Eva full_name: Käsper, Eva last_name: Käsper - first_name: Alena full_name: Kozlova, Alena id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D last_name: Kozlova - first_name: Kasumi full_name: Kishi, Kasumi id: 3065DFC4-F248-11E8-B48F-1D18A9856A87 last_name: Kishi - first_name: Ilaria full_name: Chiaradia, Ilaria id: B6467F20-02D0-11E9-BDA5-E960C241894A last_name: Chiaradia orcid: 0000-0002-9529-4464 - first_name: Kyung full_name: Noh, Kyung last_name: Noh - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: 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 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 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. 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. 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. 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. date_created: 2018-12-11T11:44:05Z date_published: 2018-11-19T00:00:00Z date_updated: 2024-03-27T23:30:44Z day: '19' ddc: - '570' department: - _id: GaNo - _id: EdHa doi: 10.1038/s41593-018-0266-2 external_id: isi: - '000451324700010' file: - access_level: open_access checksum: 60abd0f05b7cdc08a6b0ec460884084f content_type: application/pdf creator: dernst date_created: 2019-04-09T07:41:57Z date_updated: 2020-07-14T12:45:58Z file_id: '6255' file_name: 2017_NatureNeuroscience_Deliu.pdf file_size: 8167169 relation: main_file file_date_updated: 2020-07-14T12:45:58Z has_accepted_license: '1' intvolume: ' 21' isi: 1 issue: '12' language: - iso: eng month: '11' oa: 1 oa_version: Submitted Version page: 1717 - 1727 project: - _id: 254BA948-B435-11E9-9278-68D0E5697425 grant_number: '401299' name: Probing development and reversibility of autism spectrum disorders publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '8054' pubrep_id: '1071' quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/ record: - id: '6074' relation: popular_science status: public - id: '12364' relation: dissertation_contains status: public scopus_import: '1' status: public title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 21 year: '2018' ... --- _id: '529' 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. 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. author: - first_name: Florin full_name: Gherghina, Florin L last_name: Gherghina - first_name: Andrei full_name: Tica, Andrei A last_name: Tica - first_name: Elena full_name: Elena Deliu id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Mary full_name: Abood, Mary E last_name: Abood - first_name: G. full_name: Brailoiu, G. Christina last_name: Brailoiu - first_name: Eugen full_name: Brǎiloiu, Eugen last_name: Brǎiloiu citation: 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 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 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. 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. 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. short: F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, E. Brǎiloiu, Brain Research 1657 (2017) 297–303. date_created: 2018-12-11T11:46:59Z date_published: 2017-02-15T00:00:00Z date_updated: 2021-01-12T08:01:26Z day: '15' doi: 10.1016/j.brainres.2016.12.026 extern: 1 intvolume: ' 1657' month: '02' page: 297 - 303 publication: Brain Research publication_status: published publisher: Elsevier publist_id: '7290' quality_controlled: 0 status: public title: Effects of VPAC1 activation in nucleus ambiguus neurons type: journal_article volume: 1657 year: '2017' ... --- _id: '634' abstract: - lang: eng 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. alternative_title: - ADVSANAT author: - first_name: Jan full_name: Schroeder, Jan last_name: Schroeder - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Michael full_name: Schmeisser, Michael last_name: Schmeisser citation: 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' 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 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. 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. 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.' 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_created: 2018-12-11T11:47:37Z date_published: 2017-05-28T00:00:00Z date_updated: 2021-01-12T08:07:08Z day: '28' department: - _id: GaNo doi: 10.1007/978-3-319-52498-6_10 editor: - first_name: Michael full_name: Schmeisser, Michael last_name: Schmeisser - first_name: Tobias full_name: Boekers, Tobias last_name: Boekers intvolume: ' 224' language: - iso: eng month: '05' oa_version: None page: 189 - 211 project: - _id: 25473368-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: F03523 name: Transmembrane Transporters in Health and Disease publication: Translational Anatomy and Cell Biology of Autism Spectrum Disorder publication_identifier: eisbn: - 978-3-319-52498-6 publication_status: published publisher: Springer publist_id: '7156' quality_controlled: '1' scopus_import: 1 series_title: Advances in Anatomy Embryology and Cell Biology status: public title: Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 224 year: '2017' ... --- _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. acknowledgement: This work was supported by the National Institutes of Health grants DA035926 (to MEA), and P30DA013429 (to EMU). article_processing_charge: No article_type: original author: - first_name: Gabriela full_name: Brailoiu, Gabriela last_name: Brailoiu - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Jeffrey full_name: Barr, Jeffrey last_name: Barr - first_name: Linda full_name: Console Bram, Linda last_name: Console Bram - first_name: Alexandra full_name: Ciuciu, Alexandra last_name: Ciuciu - first_name: Mary full_name: Abood, Mary last_name: Abood - first_name: Ellen full_name: Unterwald, Ellen last_name: Unterwald - first_name: Eugen full_name: Brǎiloiu, Eugen last_name: Brǎiloiu citation: 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 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 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. 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. 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. 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. date_created: 2018-12-11T11:48:05Z date_published: 2017-09-01T00:00:00Z date_updated: 2021-01-12T08:12:00Z day: '01' department: - _id: GaNo doi: 10.1016/j.drugalcdep.2017.04.015 external_id: pmid: - '28623807' intvolume: ' 178' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797705 month: '09' oa: 1 oa_version: Submitted Version page: 7 - 14 pmid: 1 publication: Drug and Alcohol Dependence publication_identifier: issn: - '03768716' publication_status: published publisher: Elsevier publist_id: '6967' quality_controlled: '1' scopus_import: 1 status: public title: HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 178 year: '2017' ... --- _id: '747' abstract: - lang: eng 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. article_processing_charge: No article_type: original author: - first_name: Eugen full_name: Brǎiloiu, Eugen last_name: Brǎiloiu - first_name: Matthew full_name: Mcguire, Matthew last_name: Mcguire - first_name: Shadaria full_name: Shuler, Shadaria last_name: Shuler - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Jeffrey full_name: Barr, Jeffrey last_name: Barr - first_name: Mary full_name: Abood, Mary last_name: Abood - first_name: Gabriela full_name: Brailoiu, Gabriela last_name: Brailoiu citation: 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 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 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. ieee: E. Brǎiloiu et al., “Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus,” Neuroscience, vol. 365. Elsevier, pp. 23–32, 2017. 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. 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. short: E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu, Neuroscience 365 (2017) 23–32. date_created: 2018-12-11T11:48:17Z date_published: 2017-12-04T00:00:00Z date_updated: 2023-09-27T12:26:59Z day: '04' department: - _id: GaNo doi: 10.1016/j.neuroscience.2017.09.034 external_id: isi: - '000415966200003' pmid: - '28951324' intvolume: ' 365' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458 month: '12' oa: 1 oa_version: Submitted Version page: 23 - 32 pmid: 1 publication: Neuroscience publication_identifier: issn: - '03064522' publication_status: published publisher: Elsevier publist_id: '6911' quality_controlled: '1' scopus_import: '1' status: public title: Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 365 year: '2017' ... --- _id: '1183' abstract: - lang: eng 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. 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" article_processing_charge: No article_type: original author: - first_name: Dora-Clara full_name: Tarlungeanu, Dora-Clara id: 2ABCE612-F248-11E8-B48F-1D18A9856A87 last_name: Tarlungeanu - first_name: Elena full_name: Deliu, Elena id: 37A40D7E-F248-11E8-B48F-1D18A9856A87 last_name: Deliu orcid: 0000-0002-7370-5293 - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Majdi full_name: Kara, Majdi last_name: Kara - first_name: Philipp full_name: Janiesch, Philipp last_name: Janiesch - first_name: Mariafrancesca full_name: Scalise, Mariafrancesca last_name: Scalise - first_name: Michele full_name: Galluccio, Michele last_name: Galluccio - first_name: Mateja full_name: Tesulov, Mateja last_name: Tesulov - first_name: Emanuela full_name: Morelli, Emanuela id: 3F4D1282-F248-11E8-B48F-1D18A9856A87 last_name: Morelli - first_name: Fatma full_name: Sönmez, Fatma last_name: Sönmez - first_name: Kaya full_name: Bilgüvar, Kaya last_name: Bilgüvar - first_name: Ryuichi full_name: Ohgaki, Ryuichi last_name: Ohgaki - first_name: Yoshikatsu full_name: Kanai, Yoshikatsu last_name: Kanai - first_name: Anide full_name: Johansen, Anide last_name: Johansen - first_name: Seham full_name: Esharif, Seham last_name: Esharif - first_name: Tawfeg full_name: Ben Omran, Tawfeg last_name: Ben Omran - first_name: Meral full_name: Topcu, Meral last_name: Topcu - first_name: Avner full_name: Schlessinger, Avner last_name: Schlessinger - first_name: Cesare full_name: Indiveri, Cesare last_name: Indiveri - first_name: Kent full_name: Duncan, Kent last_name: Duncan - first_name: Ahmet full_name: Caglayan, Ahmet last_name: Caglayan - first_name: Murat full_name: Günel, Murat last_name: Günel - first_name: Joseph full_name: Gleeson, Joseph last_name: Gleeson - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: 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 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 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. 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. 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. 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. date_created: 2018-12-11T11:50:35Z date_published: 2016-12-01T00:00:00Z date_updated: 2024-03-27T23:30:12Z day: '01' ddc: - '576' - '616' department: - _id: GaNo doi: 10.1016/j.cell.2016.11.013 file: - access_level: open_access checksum: 7fe01ab12a6610d3db421e0136db2f77 content_type: application/pdf creator: system date_created: 2018-12-12T10:13:44Z date_updated: 2020-07-14T12:44:37Z file_id: '5030' file_name: IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf file_size: 73907957 relation: main_file file_date_updated: 2020-07-14T12:44:37Z has_accepted_license: '1' intvolume: ' 167' issue: '6' language: - iso: eng month: '12' oa: 1 oa_version: Submitted Version page: 1481 - 1494 project: - _id: 25473368-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: F03523 name: Transmembrane Transporters in Health and Disease publication: Cell publication_status: published publisher: Cell Press publist_id: '6170' pubrep_id: '771' quality_controlled: '1' related_material: record: - id: '395' relation: dissertation_contains status: public scopus_import: '1' status: public title: Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder type: journal_article user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 volume: 167 year: '2016' ...