title: Voluntary exercise followed by chronic stress strikingly increases mature adult-born hippocampal neurons and prevents stress-induced deficits in 'what-when-where' memory.
abstract: We investigated whether voluntary exercise prevents the deleterious effects of chronic stress on episodic-like memory and adult hippocampal neurogenesis. After bromodeoxyuridine (BrdU) administration, mice were assigned to receive standard housing, chronic intermittent restraint stress, voluntary exercise or a combination of both (stress starting on the seventh day of exercise). Twenty-four days later, mice were tested in a 'what-when-where' object recognition memory task. Adult hippocampal neurogenesis (proliferation, differentiation, survival and apoptosis) and c-Fos expression in the hippocampus and extra-hippocampal areas (medial prefrontal cortex, amygdala, paraventricular hypothalamic nucleus, accumbens and perirhinal cortex) were assessed after behavior. Chronic intermittent restraint stress impaired neurogenesis and the 'when' memory, while exercise promoted neurogenesis and improved the 'where' memory. The 'when' and 'where' memories correlated with c-Fos expression in CA1 and the dentate gyrus, respectively. Furthermore, analysis suggested that each treatment induced a distinct pattern of functional connectivity among the areas analyzed for c-Fos. In the animals in which stress and exercise were combined, stress notably reduced the amount of voluntary exercise performed. Nevertheless, exercise still improved memory and counteracted the stress induced-deficits in neurogenesis and behavior. Interestingly, compared with the other three treatments, the stressed exercising animals showed a larger increase in cell survival, the maturation of new neurons and apoptosis in the dentate gyrus, with a considerable increase in the number of 24-day-old BrdU+cells that differentiated into mature neurons. The interaction between exercise and stress in enhancing the number of adult-born hippocampal neurons supports a role of exercise-induced neurogenesis in stressful conditions.
authors: Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), Spain. Electronic address: estela.castilla@fundacionimabis.org.
authors: Estela
authors: E
authors: Castilla-Ortega
authors: Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Universidad de Málaga, and Instituto de Investigación Biomédica de Málaga (IBIMA), E-29071 Málaga, Spain.
authors: Cristina
authors: C
authors: Rosell-Valle
authors: Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Universidad de Málaga, and Instituto de Investigación Biomédica de Málaga (IBIMA), E-29071 Málaga, Spain.
authors: Carmen
authors: C
authors: Pedraza
authors: Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), Spain.
authors: Fernando
authors: F
authors: Rodríguez de Fonseca
authors: Unidad de Microscopía and Unidad de Gestión Clínica de Neurociencias, Hospital Regional Universitario Carlos Haya, Instituto de Investigación Biomédica de Málaga (IBIMA), E-29009 Málaga, Spain.
authors: Guillermo
authors: G
authors: Estivill-Torrús
authors: Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Universidad de Málaga, and Instituto de Investigación Biomédica de Málaga (IBIMA), E-29071 Málaga, Spain. Electronic address: luis@uma.es.
authors: Luis J
authors: LJ
authors: Santín
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*
keywords: Adult hippocampal neurogenesis; Episodic-like memory; Functional networks; Intermittent restraint stress; Object recognition; c-Fos