Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1

Neurotrophic factors and growth factors are known to have positive effects on hippocampal proliferation. However, previous findings on the effects of these factors on exercise-induced hippocampal proliferation are inconsistent. In this study, we investigated the effects of voluntary running on hippocampal proliferation and the expression levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) in hippocampus. Twenty-four male C57BL/6 mice were randomly divided into four groups: control groups 1 and 2 (C1, n = 6; C2, n = 6) and running groups 1 and 2 (R1, n = 6; R2, n = 6). Mice from C1 and C2 were placed individually in standard cages for eight weeks; mice from R1 and R2 were housed individually in cages with a running wheel for eight weeks. At the fifth week, C1 and R1 mice were injected with BrdU for 7 consecutive days. On the first day of the ninth week, the C1 and R1 mice were anaesthetized and hippocampal neuronal proliferation was assessed using immunohistochemistry; the mice in C2 and R2 were sacrificed to test the expression levels of NGF, BDNF, and IGF-1 mRNA in hippocampus using RT-PCR. The results indicated that voluntary running significantly increased the number of BrdU-positive cells in the dentate gyrus (DG), and significantly upregulated the levels of NGF, BDNF, and IGF-1 mRNA in the hippocampus. In conclusion, our findings indicated that hippocampal proliferation was enhanced by voluntary running, which was associated with increased NGF, BDNF, and IGF-1 mRNA levels in the hippocampus.