title: Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice.
abstract: Chronic stress is known to induce not only anxiety and depressive-like phenotypes in mice but also cognitive impairments, for which the action of classical antidepressant compounds remains unsatisfactory. In this context, we investigated the effects of chronic social defeat stress (CSDS) on anxiety-, social- and cognitive-related behaviors, as well as hippocampal Bdnf, synaptic plasticity markers (PSD-95, Synaptophysin, Spinophilin, Synapsin I and MAP-2), and epigenetic modifying enzymes (MYST2, HDAC2, HDAC6, MLL3, KDM5B, DNMT3B, GADD45B) gene expression in C57BL/6J mice. CSDS for 10 days provoked long-lasting anxious-like phenotype in the open field and episodic memory deficits in the novel object recognition test. While total Bdnf mRNA level was unchanged, Bdnf exon IV, MAP-2, HDAC2, HDAC6 and MLL3 gene expression was significantly decreased in the CSDS mouse hippocampus. In CSDS mice treated 3 weeks with 50 mg/kg/d agomelatine, an antidepressant with melatonergic receptor agonist and 5-HT2Creceptor antagonist properties, the anxious-like phenotype was not reversed, but the treatment successfully prevented the cognitive impairments and hippocampal gene expression modifications. Altogether, these data evidenced that, in mice, agomelatine was effective in alleviating stress-induced altered cognitive functions, possibly through a mechanism involving BDNF signaling, synaptic plasticity and epigenetic remodeling.
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Martin
authors.affiliation: Centre de NeuroImagerie de Recherche - CENIR- Inserm UMR1127- CNRS 7225, Institut Cerveau Moelle - ICM, Sorbonne Universités, UPMC UMR S 1127, Paris, France.
authors.forename: Najib
authors.initials: N
authors.lastname: Allaïli
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Euvrard
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
authors.forename: Tevrasamy
authors.initials: T
authors.lastname: Marday
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
authors.forename: Armance
authors.initials: A
authors.lastname: Riffaud
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Franc
authors.affiliation: Institut de Recherches Internationales Servier, IRIS, Suresnes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaër
authors.affiliation: Institut de Recherches Internationales Servier, IRIS, Suresnes, France.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Social and Affective Neuroscience - SAN Laboratory - Inserm U 1127- CNRS UMR 7225- Institut du Cerveau et de la Moelle- ICM - Sorbonne Universités, UPMC UMR S 1127, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fossati
authors.affiliation: Centre de NeuroImagerie de Recherche - CENIR- Inserm UMR1127- CNRS 7225, Institut Cerveau Moelle - ICM, Sorbonne Universités, UPMC UMR S 1127, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehericy
authors.affiliation: Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Université Paris Descartes, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lanfumey
mesh_terms: D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D013315:Stress, Psychological / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016704:Synapsins / Q000235:genetics; D016708:Synaptophysin / Q000235:genetics; D000099273:Neurabins; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016704:Synapsins; D016708:Synaptophysin; D000099273:Neurabins; C501447:Dlg4 protein, mouse; C084711:agomelatine; D009281:Naphthalenes