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Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice.
Sarrazin, David H; Gardner, Wilf; Marchese, Carole; Balzinger, Martin; Ramanathan, Chockalingam; Schott, Marion; Rozov, Stanislav; Veleanu, Maxime; Vestring, Stefan; Normann, Claus; Rantamäki, Tomi; Antoine, Benedicte; Barrot, Michel; Challet, Etienne; Bourgin, Patrice; Serchov, Tsvetan.
Afiliación
  • 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.
  • Marchese C; 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.
  • Ramanathan C; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France.
  • 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; University of Strasbourg Institute for Advanced Study (USIAS), University of Strasbourg, Strasbourg, France.
  • Veleanu M; Institute for Physiology I, University of Freiburg, Medical Faculty, Freiburg, Germany.
  • Vestring S; Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Institute of Cellular and Integrative Neurosciences (INCI) UPR 3212, Strasbourg, France.
  • Normann C; Laboratory of Neurotherapeutics, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
  • Rantamäki T; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Antoine B; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Barrot M; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Challet E; Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Bourgin P; Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Serchov T; Center for Neuromodulation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nat Commun ; 15(1): 7257, 2024 Aug 23.
Article en En | MEDLINE | ID: mdl-39179578
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corteza Prefrontal / Ratones Noqueados / Depresión / Factores de Transcripción ARNTL / Ketamina / Antidepresivos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corteza Prefrontal / Ratones Noqueados / Depresión / Factores de Transcripción ARNTL / Ketamina / Antidepresivos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido