Physical exercise promotes proliferation and differentiation of endogenous neural stem cells via ERK in rats with cerebral infarction.

Abstract

Physical exercise is beneficial for the functional recovery of neurons after stroke. It has been suggested that exercise regulates proliferation and differentiation of endogenous neural stem cells (NSCs); however, the underlying molecular mechanisms are still largely unknown. In the present study, the aim was to investigate whether physical exercise activates the extracellular signal-regulated kinase (ERK) signaling pathway to promote proliferation and differentiation of NSCs in rats with cerebral infarction, thereby improving neurological function. Following middle cerebral artery occlusion, rats underwent physical exercise and neurological behavior was analyzed at various time points. Immunofluorescence staining was performed to detect proliferation and differentiation of NSCs, and western blotting was used to analyze cyclin-dependent kinase 4 (CDK4), Cyclin D1, retinoblastoma protein (p-Rb), P-16, phosphorylated (p)-ERK1/2 and c-Fos expression. The results indicated that physical exercise promoted proliferation and differentiation of NSCs, and led to improved neural function. In addition, the expression levels of CDK4, Cyclin D1, p-Rb, p-ERK1/2 and c-Fos were upregulated, whereas the expression of P-16 was downregulated following exercise. U0126, an inhibitor of ERK signaling, reversed the beneficial effects of exercise. Therefore, it may be hypothesized that physical exercise enhances proliferation and differentiation of endogenous NSCs in the hippocampus of rats with cerebral infarction via the ERK signaling pathway.