Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety
Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety
SUMMARY Recently, oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including general anxiety disorder or autism spectrum disorder. Therefore, knowledge on the involved molecular processes downstream of OXT receptor (OXTR) activation is indispensable. We reveal that alternative splicing of corticotropin releasing factor receptor 2α (CRFR2α) parallels increased anxiety-like behavior following chronic OXT treatment, contrasting the well-known anxiolysis of acute OXT. In detail, chronic OXT shifts the splicing ratio between membrane-bound (mCRFR2α) and soluble CRFR2α (sCRFR2α) in favor of the latter via ERK1/2-MEF2A signaling. Targeted manipulations of Crfr2α splicing mimic the effect of chronic OXT, confirming its role in the regulation of anxiety-like behavior. Furthermore, chronic OXT triggers cytoplasmic distribution and extracellular release of sCRFR2α into the cerebrospinal fluid, with sCRFR2α levels positively correlating with anxiety-like behavior. Concluding, the dichotomy between anxiolytic mCRFR2α and anxiogenic sCRFR2α is the basis for the deleterious effects of chronic OXT on anxiety. Graphical Abstractbiorxiv;2020.08.19.255844v1/UFIG1F1ufig1
Peters Sebastian、Schmidtner Anna K.、Kuffner Kerstin、Stang Simone、Bosch Oliver J.、van den Burg Erwin H.、Jurek Benjamin、Berger Ilona、Royer Melanie、Reber Stefan O.、Bludau Anna、Winter Julia、Langgartner Dominik、Meyer Magdalena、Bianchi Marta、Neumann Inga D.、Slattery David A.、Hartmann Finn
Department of Neurology, University Hospital RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgCentre de Neurosciences Psychiatriques, LausanneDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of Regensburg||Institute for Molecular and Cellular Anatomy, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgLaboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, University of UlmDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgLaboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, University of UlmDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of RegensburgGroup of Translational Psychiatry, Klinik f¨1r Psychiatrie, Psychosomatik und Psychotherapie, University Hospital Frankfurt am MainDepartment of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of Regensburg
神经病学、精神病学基础医学分子生物学
chronic oxytocinalternative splicingsCRFR2MEF2AanxietystressPVNHiBiTGapmeRs
Peters Sebastian,Schmidtner Anna K.,Kuffner Kerstin,Stang Simone,Bosch Oliver J.,van den Burg Erwin H.,Jurek Benjamin,Berger Ilona,Royer Melanie,Reber Stefan O.,Bludau Anna,Winter Julia,Langgartner Dominik,Meyer Magdalena,Bianchi Marta,Neumann Inga D.,Slattery David A.,Hartmann Finn.Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety[EB/OL].(2025-03-28)[2025-05-06].https://www.biorxiv.org/content/10.1101/2020.08.19.255844.点此复制
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