title: The neurogenic effects of an enriched environment and its protection against the behavioral consequences of chronic mild stress persistent after enrichment cessation in six-month-old female Balb/C mice.
abstract: Because stress may underlie the presence of depressive episodes, strategies to produce protection against or to reverse the effects of stress on neuroplasticity and behavior are relevant. Preclinical studies showed that exposure to stimuli, such as physical activity and environmental enrichment (ENR), produce beneficial effects against stress causing antidepressant-like effects in rodents. Additionally, ENR induces positive effects on neuroplasticity, neurochemistry and behavior at any age of rodents tested. Here, we analyzed whether ENR exposure prevents the development of depressive-like behavior produced by unpredictable, chronic mild stress (CMS) exposure as well as changes in hippocampal neurogenesis in a six-month-old female Balb/C mice, strain that shows low baseline levels of hippocampal neurogenesis. Mice were assigned to one of four groups: (1) normal housing-normal housing (NH-NH), (2) NH-CMS, (3) ENR-NH, or (4) ENR-CMS. The animals were exposed over 46 days to ENR or NH and subsequently to NH or CMS for 4 weeks. ENR induces long-term effects protecting against CMS induction of anhedonia and hopelessness behaviors. Independent of housing conditions, ENR increased the number of proliferative cells (Ki67), and CMS decreased the number of proliferative cells. ENR increased the newborn cells (BrdU) and mature phenotypes of neurons; these effects were not changed by CMS exposure. Similarly, the number of doublecortin-positive cells was not affected by CMS in ENR mice, which showed more cells with complex dendrite arborizations. Our study suggests that ENR induces protection against the effects of CMS on behavior and neuroplasticity in six-month-old Balb/C mice.
authors.affiliation: Laboratory of Neuropsychopharmacology, Division of Neurosciences, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México, D.F., Mexico.
authors.forename: Nelly Maritza
authors.initials: NM
authors.lastname: Vega-Rivera
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, 14370 México, D.F., Mexico.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ortiz-López
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, 14370 México, D.F., Mexico.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Gómez-Sánchez
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, 14370 México, D.F., Mexico.
authors.forename: Julian
authors.initials: J
authors.lastname: Oikawa-Sala
authors.affiliation: Laboratory of Neuropsychopharmacology, Division of Neurosciences, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México, D.F., Mexico. Electronic address: estrada@imp.edu.mx.
authors.forename: Erika Monserrat
authors.initials: EM
authors.lastname: Estrada-Camarena
authors.affiliation: Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada México-Xochimilco 101, 14370 México, D.F., Mexico. Electronic address: gbernabe@imp.edu.mx.
authors.forename: Gerardo Bernabé
authors.initials: GB
authors.lastname: Ramírez-Rodríguez
mesh_terms: D059445:Anhedonia / Q000502:physiology; D000818:Animals; D001774:Blood Chemical Analysis; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000502:physiology; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology; D003866:Depressive Disorder / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000089622:Doublecortin Domain Proteins; D004777:Environment; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006799:Housing, Animal; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine; D003345:Corticosterone
keywords: Adult neurogenesis; Chronic mild stress; Corticosterone; Depression; Doublecortin; Hippocampus