Fiche publication
Date publication
août 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARROT Michel
Tous les auteurs :
Sarrazin DH, Gardner W, Marchese C, Balzinger M, Ramanathan C, Schott M, Rozov S, Veleanu M, Vestring S, Normann C, Rantamäki T, Antoine B, Barrot M, Challet E, Bourgin P, Serchov T
Lien Pubmed
Résumé
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.
Mots clés
Animals, Prefrontal Cortex, metabolism, Depression, drug therapy, Mice, Antidepressive Agents, pharmacology, Male, Ketamine, pharmacology, Mice, Knockout, ARNTL Transcription Factors, metabolism, Circadian Rhythm, drug effects, Mice, Inbred C57BL, Period Circadian Proteins, metabolism, Disease Models, Animal, Phenotype, Neuronal Plasticity, drug effects, Receptors, AMPA, metabolism, Nuclear Receptor Subfamily 1, Group D, Member 1, metabolism, Homer Scaffolding Proteins, metabolism, Neurons, metabolism
Référence
Nat Commun. 2024 08 23;15(1):7257
