Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice.

Autor: Sarrazin DH; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France., Gardner W; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France.; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France., Marchese C; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France.; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France., Balzinger M; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France.; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France., Ramanathan C; Institute for Physiology I, University of Freiburg, Medical Faculty, Freiburg, Germany., Schott M; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France., Rozov S; Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Veleanu M; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Vestring S; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Normann C; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Neuromodulation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Rantamäki T; Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Antoine B; Sorbonne Université, INSERM, Centre de Recherches St-Antoine (CRSA), Paris, France., Barrot M; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France.; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France., Challet E; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France., Bourgin P; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France.; CIRCSom (International Research Center for ChronoSomnology) & Sleep Disorders Center, Strasbourg University Hospital, Strasbourg, France., Serchov T; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France. serchov@inci-cnrs.unistra.fr.; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France. serchov@inci-cnrs.unistra.fr.; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. serchov@inci-cnrs.unistra.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 23; Vol. 15 (1), pp. 7257. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1038/s41467-024-51716-9
Abstrakt: Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects. Per2 silencing in mPFC produced antidepressant-like effects, while REV-ERB agonism enhanced the depression-like phenotype and suppressed ketamine action. Pharmacological potentiation of clock positive modulator ROR elicited antidepressant-like effects, upregulating plasticity protein Homer1a, synaptic AMPA receptors expression and plasticity-related slow wave activity specifically in the mPFC. Our data demonstrate a critical role for mPFC molecular clock in regulating depression-like behavior and the therapeutic potential of clock pharmacological manipulations influencing glutamatergic-dependent plasticity.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: