title: Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin.
abstract: Environmental enrichment (EE) that combines voluntary physical exercise, sensory and social stimuli, causes profound changes in rodent brain at molecular, anatomical and behavioral levels. Here, we show that EE efficiently reduces anxiety and depression-like behaviors in a mouse model of depression induced by long-term administration of corticosterone. Mechanisms underlying EE-related beneficial effects remain largely unexplored; however, our results point toward adiponectin, an adipocyte-secreted protein, as a main contributor. Indeed, adiponectin-deficient (adipo(-/-)) mice did not benefit from all the EE-induced anxiolytic and antidepressant-like effects as evidenced by their differential responses in a series of behavioral tests. Conversely, a single intravenous injection of exogenous adiponectin restored the sensitivity of adipo(-/-) mice to EE-induced behavioral benefits. Interestingly, adiponectin depletion did not prevent the hippocampal neurogenesis induced by EE. Therefore, antidepressant properties of adiponectin are likely to be related to changes in signaling in the hypothalamus rather than through hippocampal-neurogenesis mechanisms. Additionally, EE did not modify the plasma levels of adiponectin but may favor the passage of adiponectin from the blood to the cerebrospinal fluid. Our findings provide advances in the understanding of the anxiolytic and antidepressant-like effects of EE and highlight adiponectin as a pivotal mediator.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nicolas
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Veyssière
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Gandin
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Zsürger
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Mariel
authors.initials: M
authors.lastname: Pietri
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Heurteaux
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Glaichenhaus
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Petit-Paitel
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 7275, Centre National de la Recherche Scientifique 660, route des lucioles, 06560 Valbonne, France; Université de Nice Sophia Antipolis, 28, avenue Valrose, 06103 Nice, France. Electronic address: chabry@ipmc.cnrs.fr.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Chabry
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000827:Animal Welfare; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology / Q000628:therapy*; D000067290:Behavior Rating Scale; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000378:metabolism / Q000523:psychology / Q000628:therapy*; D004780:Environment, Controlled; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology*; D011897:Random Allocation
chemical_list: D052242:Adiponectin; D003345:Corticosterone
keywords: Adiponectin; Anxiety; Behavior; Depression; Enriched environment; Neurogenesis