Running reduces stress and enhances cell genesis in aged mice

Abstract

Cell proliferation and neurogenesis are diminished in the aging mouse dentate gyrus. However, it is not known whether isolated or social living affects cell genesis and stress levels in old animals. To address this question, aged (17-18 months old) female C57Bl/6 mice were single or group housed, under sedentary or running conditions. We demonstrate that both individual and socially housed aged C57Bl/6 mice have comparable basal cell proliferation levels and demonstrate increased running-induced cell genesis. To assess stress levels in young and aged mice, corticosterone (CORT) was measured at the onset of the active/dark cycle and 4h later. In young mice, no differences in CORT levels were observed as a result of physical activity or housing conditions. However, a significant increase in stress in socially housed, aged sedentary animals was observed at the onset of the dark cycle; CORT returned to basal levels 4h later. Together, these results indicate that voluntary exercise reduces stress in group housed aged animals and enhances hippocampal cell proliferation.

Fig. 1.

Voluntary exercise promotes cellular proliferation, irrespective of housing condition, in the aged mouse dentate gyrus. (A) Schematic diagram of the experimental paradigm and BrdU injection protocol. Exercising mice were allowed access to running wheels for 11 days. BrdU (50 mg/kg) was administered daily and mice were perfused on day 11. (B) Representative pictures of BrdU-positive cells in the dentate gyrus of individual sedentary controls (I-CON), individual runners (I-RUN), social sedentary controls (S-CON), and social runners (S-RUN). Scale bar: 50 μm. (C) Individual and social exercising groups (black bars) demonstrate increases in the amount of BrdU-positive cells in comparison to their sedentary controls (white bars). (*) Denotes significance (p < 0.05) in comparison to sedentary controls; (**) denotes significance (p < 0.05) in comparison to all other experimental groups. (D) Average running distance per cage during the 11-day exercise period for young and aged, individually and socially housed running animals. (*) and (**) denote significance (p < 0.05) in comparison to young individual runners and young social runners, respectively. Error bars represent S.E.M.

Fig. 2.

Corticosterone levels of young and aged mice. (A, B) In young mice no change in CORT was observed as a result of housing or exercise conditions. (C) Aged, socially housed, sedentary mice, have significantly higher stress levels than all other aged mice at active cycle onset. In addition, aged group housed runners have lower CORT levels than their young counterparts. (D) Four hours into active cycle, CORT levels of aged animals show no change as a result of exercise or housing condition. CORT levels in young Internal Controls that did not receive BrdU injections, are depicted with both young (A, B) and aged (C, D) groups. Error bars represent S.E.M. (**) Denotes significance in comparison to all other aged groups at the onset of the active cycle; (*) denotes a significant difference between young and aged grouped runners (p < 0.05).