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

First Author  Zhao N Year  2018
Journal  Neuroreport Volume  29
Issue  10 Pages  819-825
PubMed ID  29672446 Mgi Jnum  J:351918
Mgi Id  MGI:7703875 Doi  10.1097/WNR.0000000000001038
Citation  Zhao N, et al. (2018) The effects of treadmill exercise on autophagy in hippocampus of APP/PS1 transgenic mice. Neuroreport 29(10):819-825
abstractText  The beta-amyloid (Abeta) deposition is one of the major pathological hallmark of Alzheimer's disease. Dysfunction in autophagy has been reported to lead to the Abeta deposition. The current study aimed to investigate the effects of treadmill exercise on autophagy activity and the Abeta deposition and to demonstrate whether exercise-induced reduction in the Abeta 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 Abeta plaques and soluble forms of Abeta, autophagy markers light chain 3 and P62, and lysosomal marker lysosome-associated membrane protein 1 (Lamp1) were measured in the hippocampus. Both Abeta plaques and soluble forms of Abeta (Abeta40 and Abeta42) were significantly increased in TG-SED mice compared with WT-SED mice, whereas exercise reduced Abeta 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 Abeta deposition by enhancing autophagy-lysosomal activity in APP/PS1 transgenic mice, demonstrating a possible approach in Alzheimer's disease prevention and treatment.
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