The Effects of Aerobic Exercise on Tau Phosphorylation and PI3K/Akt Pathway in the Hippocampus of Obese Rats / 中国运动医学杂志

ABSTRACT

Objective To investigate the effects of aerobic exercise on tau phosphorylation and PI3K/ Akt pathway in the hippocampus of obese rats,and provide some theoretical basis for physical activity improving obesity-related neurological disorders.Methods Male Sprague-Dawley rats aged 3 weeks were randomly assigned to either a high-fat or a normal diet protocol for 12 weeks.Animals submitted to the high-fat diet were further divided into two groupsa sedentary group (HF-Sed) and an exercise group (HF-Ex).The rats fed the normal diet were also divided into a sedentary group (ND-Sed)and an exercise group (ND-Ex).The rats in the HF-Ex and ND-Ex groups underwent a treadmill training for 8 weeks.Then the hippocampus was isolated at 48h after the last exercise.The protein and phosphorylation levels of tau,glycogen synthase kinase 3β (GSK3β),phosphoinositide 3-kinase (PI3K) and Akt were assayed using Western blotting.Results After 12 weeks of feeding,55％ of rats in the high-fat diet group reached the conditions for the obesity model.After 8 weeks of treadmill exercises,in the HF-Sed group the phosphorylation level of tau was significanlty higher than that in the ND-Sed group,while in the HF-Ex group that was significantly lower than the HF-Sed group.Moreover,in the HF-Sed group the phosphorylation level of GSK3β Ser9 was significantly lower,and the phosphorylation level of GSK3β Tyr216 was significantly higher than the ND-Sed group,indicating the activity of GSK3β was significantly higher than the ND-Sed group.However,after 8 weeks of treadmill exercise,in the HF-Ex group the phosphorylation level of GSK3β Ser9 was signfiicantly higher,and the phosphorylation level of GSK3β Tyr216 was signficanlty lower than the HF-Sed group,indicating significantly lower activity of GSK3β than the HF-Sed group.Then,in the HF-Sed group the protein levels of PI3K p110 and p85 subunits,and the phosphorylation levels of Akt Thr308 and Ser473 were significantly lower than those in the ND-Sed group,indicating inhibited activity of the PI3K/Akt pathway.However,in the HF-Ex group the protein levels of PI3K p110 and p85 subunits and the phosphorylation levels of Akt Thr308 and Ser473 were significanlty higher than those in the HF-Sed group,showing the activity of PI3K/Akt pathway was enhanced.Conclusion Obesity induces tau hyperphosphorylation in the rats hippocampus and long-term aerobic exercises can reduce tau hyperphosphorylation by increasing PI3K/Akt pathway activity and inhibiting GSK3β activity.It has a positive effect on delaying the formation of neurofibrillary tangles and improving obesity-related neurological disorders.