Treadmill exercise promotes neurogenesis and myelin repair via upregulating Wnt/β–catenin signaling pathways in the juvenile brain following focal cerebral ischemia/reperfusion

Abstract

Physical exercise has a neuroprotective effect and is an important treatment after ischemic stroke. Promoting neurogenesis and myelin repair in the penumbra is an important method for the treatment of ischemic stroke. However, the role and potential mechanism of exercise in neurogenesis and myelin repair still needs to be clarified. The goal of the present study was to ascertain the possible effect of treadmill training on the neuroprotective signaling pathway in juvenile rats after ischemic stroke. The model of middle cerebral artery occlusion (MCAO) in juvenile rats was established and then the rats were randomly divided into 9 groups. XAV939 (an inhibitor of the Wnt/β–catenin pathway) was used to confirm the effects of the Wnt/β-catenin signaling pathway on exercise-mediated neurogenesis and myelin repair. Neurological deficits were detected by modified neurological severity score, the injury of brain tissue and the morphology of neurons was detected by hematoxylin-eosin staining and Nissl staining, and the infarct volume was detected by 2,3,5-triphenyl tetrazolium chloride staining. The changes in myelin were observed by Luxol fast blue staining. The neuron ultrastructure was observed by transmission electron microscopy. Immunofluorescence and western blots analyzed the molecular mechanisms. The results showed that treadmill exercise improved neurogenesis, enhanced myelin repair, promoted neurological function recovery and reduced infarct volume. These were the results of the upregulation of Wnt3a and nucleus β-catenin, brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP). In addition, XAV939 inhibited treadmill exercise-induced neurogenesis and myelin repair, which was consistent with the downregulation of Wnt3a, nucleus β-catenin, BDNF and MBP expression, and the deterioration of neurological function. In summary, treadmill exercise promotes neurogenesis and myelin repair by upregulating the Wnt/β-catenin signaling pathway, to improve the neurological deficit caused by focal cerebral ischemia/reperfusion.