The effects of treadmill exercise on autophagy in hippocampus of APP/PS1 transgenic mice

摘要

The -amyloid (A) deposition is one of the major pathological hallmark of Alzheimer's disease. Dysfunction in autophagy has been reported to lead to the A deposition. The current study aimed to investigate the effects of treadmill exercise on autophagy activity and the A deposition and to demonstrate whether exercise-induced reduction in the A deposition was associated with changes in autophagy activity. APP/PS1 transgenic mice were divided into transgenic sedentary (TG-SED, n=12) and transgenic exercise (TG-EXE, n=12) groups. Wild-type mice were also divided into sedentary (WT-SED, n=12) and exercise (WT-EXE, n=12) groups. The WT-EXE and TG-EXE mice were subjected to treadmill exercise for 12 weeks. The levels of A plaques and soluble forms of A, autophagy markers light chain 3 and P62, and lysosomal marker lysosome-associated membrane protein 1 (Lamp1) were measured in the hippocampus. Both A plaques and soluble forms of A (A40 and A42) were significantly increased in TG-SED mice compared with WT-SED mice, whereas exercise reduced A deposition in APP/PS1 transgenic mice. Coincidentally, TG-SED mice displayed a decrease in autophagy activity as evidenced by a significant increase in the levels of light chain 3-II and P62, as well as an accumulation of lysosome as evidenced by a significant over-expression of Lamp1. Interestingly, exercise increased autophagy activity as evidenced by a significant reduction in the levels of P62 and Lamp1 in TG-EXE mice. These findings suggest that treadmill exercise is efficient in decreasing A deposition by enhancing autophagy-lysosomal activity in APP/PS1 transgenic mice, demonstrating a possible approach in Alzheimer's disease prevention and treatment.