Stress Differentially Regulates the Effects of Voluntary Exercise on Cell Proliferation in the Dentate Gyrus of Mice

It has been well-established that cell proliferation and neurogenesis in the adult mouse dentate gyrus (DG) can be regulated by voluntary exercise. Recent evidence has suggested that the effects of voluntary exercise can in turn be influenced by environmental factors that regulate the amount of stress an animal is exposed to. In this study, we use bromodeoxyuridine and proliferating cell nuclear antigen immu- nohistochemistry to show that voluntary exercise produces a significant increase in cell proliferation in the adult mouse DG in both isolated and socially housed mice. This effect on proliferation translates into an increase in neurogenesis and neuronal branching of new neurons in the mice that exercised. Although social condition did not regulate prolifer- ation in young adult mice, an effect of social housing could be observed in mice exposed to acute restraint stress. Surprisingly, only exercising mice housed in isolated conditions showed an increase in cellular pro- liferation following restraint stress, whereas socially housed, exercising mice, failed to show a significant increase in proliferation. These findings indicate that social housing may increase the effects of any stressful episodes on hippocampal neurogenesis in the mouse DG. V C 2008 Wiley-Liss, Inc.