High intensity interval training ameliorates cognitive impairment in T2DM mice possibly by improving PI3K/Akt/mTOR Signaling-regulated autophagy in the hippocampus

Exercise can improve cognitive impairment in type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are not clear, and the optimal exercise modes for cognitive benefits are controversial. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity interval training (MICT) on cognitive function and the PI3K/Akt/mTOR pathway as well as autophagy in T2DM mice. The results showed that 8 weeks of HIIT and MICT intervention could improve the spatial learning and memory ability of T2DM mice, as determined by the Morris water maze (MWM) test. Both HIIT and MICT similarly improved autophagy, as evidenced by increased Beclin1 and LC3 II/I ratios and decreased p62. Meanwhile, HIIT and MICT inhibited excessive activation of the PI3K/Akt/mTOR pathway in the hippocampus. HIIT induced a larger reduction in mTOR activity than MICT. This study suggests that both HIIT and MICT can alleviate cognitive decline induced by T2DM, improve autophagy in the hippocampus, and downregulate the excessive activation of the PI3K/Akt/mTOR signaling pathway, with similar effects.