Voluntary wheel running reverses the decrease in subventricular zone neurogenesis caused by corticosterone

Abstract

Adult neurogenesis within the dentate gyrus of the hippocampus can be increased by voluntary exercise but is suppressed under stress, such as with corticosterone (CORT). However, the effects of exercise and corticosterone on the cell proliferation of the other traditional neurogenic site, the subventricular zone (SVZ) have been reported with controversial results. In addition, the co-treatment effects of voluntary exercise and corticosterone have not been investigated. This study aims to determine whether corticosterone can suppress cell proliferation in the SVZ, and whether this can be reversed by voluntary exercise. In the present study, the effect of chronic (4 weeks) corticosterone treatment and wheel running simultaneously on the SVZ cell proliferation of adult Sprague-Dawley rats was examined. The results showed that cell proliferation indicated by bromodeoxyuridine (BrdU) was increased by voluntary wheel running whereas it was decreased by corticosterone treatment within the SVZ of the rats without running. For the rats with both corticosterone treatment and wheel running, it was found that the number of BrdU-labeled cells was approximately at the same level as the vehicle control group. Furthermore, these proliferating cells expressed doublecortin (DCX), a migrating neuroblast marker. Wheel running increased the percentage of BrdU-labeled cells expressing DCX in the SVZ whereas corticosterone treatment decreased this percentage. Thus, chronic injection of corticosterone can decrease the number of proliferating cells while wheel running can reverse the decrease in cell proliferation within the SVZ to normal levels. In addition, corticosterone can suppress the cell differentiation within the SVZ and this was alleviated by wheel running as indicated by the double-labeling of BrdU and DCX.