Long-term treadmill exercise reduces tau hyperphosphorylation and inhibits neuronal cell apoptosis by activating the PI3K/Akt/GSK3β pathway in rat brain

Many studies suggest that regular physical exercise can reduce the risk of Alzheimer’s disease and slow its onset and progression. However, the mechanism is still unclear. Alzheimer’s disease is characterized by neurofibrillary tangle formation and neuronal loss, which are associated with tau hyperphosphorylation and neuronal cell apoptosis respectively. The PI3K/Akt/GSK3β signaling pathway regulates tau phosphorylation and neuronal cell apoptosis, and plays a pivotal role in the development of pathology in Alzheimer’s disease. Here we investigated the effect of long-term treadmill exercise on tau phosphorylation, neuronal cell apoptosis, and the PI3K/Akt/GSK3β pathway activity in the cerebral cortex and hippocampus of rats. After 8 weeks of treadmill exercise, the phosphorylation levels of tau at multiple sites including Ser202, Thr231 and Ser396 were decreased. The ratio of Bcl-2 to Bax (Bcl-2/Bax) was increased, and cleaved caspase-3 was suppressed. Furthermore, the expression of PI3K p110, the phosphorylation levels of Akt at Thr308 and Ser473 and GSK3β at Ser9 were increased. This study demonstrated that long-term treadmill exercise could reduce tau hyperphosphorylation and inhibit neuronal cell apoptosis by activating the PI3K/Akt/GSK3β pathway in rat brain