Intensity-dependent effects of consecutive treadmill exercise on spatial learning and memory through the p-CREB/BDNF/NMDAR signaling in hippocampus.

Exercise is the most recommended non-pharmacological intervention to improve neurocognitive functions under physiological and pathological conditions. However, it remains to be elucidated concerning the influence and the underlying neurological molecular mechanism of different exercise intensity on cognitive function. In this study, we aimed to explore the effects of exercise intensity on spatial learning and memory, as well as the regulation of brain-derived neurotrophic factor (BDNF)/p-CREB/NMDAR signal. In the research, low-intensity consecutive treadmill (LICT) and high-intensity consecutive treadmill (HICT) were implied to rats for 8 weeks. We found that the performances in the Morris water maze were improved in the LICT group, while reduced in the HICT group as compared with the sedentary rats. Moreover, the expression of BDNF mRNA, phosphorylation cAMP-response-element binding protein (p-CREB), mature BDNF (mBDNF), tropomyosin receptor kinase B (TrkB), tissue plasminogen activator (t-PA), and NR2B proteins was increased, whereas the expression of precursor BDNF (proBDNF) and pan-neurotrophin receptor 75 (p75(NTR)) proteins was decreased in the hippocampus of LICT group compared with the sedentary rats. On the contrary, the expression of proteins and mRNA aforementioned in the LICT group showed a reversed tendency in the hippocampus of HICT rats. These findings suggest that the consecutive low-intensity exercise and high-intensity exercise exert different effects on spatial learning and memory by oppositely regulating the mutual stimulation of p-CREB and BDNF mRNA feedback loop, as well as the t-PA/BDNF/NMDAR which is the post-translation cascades of BDNF signaling.