Cheyuk gwahag yeon-gu (Dec 2020)
Ameliorative effect of treadmill exercise on cognitive deficits and amyloid-b pathology through the mitophagy in a mouse model of Alzheimer's disease
Abstract
Purpose The aim of this study was to investigate the effects of treadmill exercise on mitochondrial quality control in the APP/sw transgenic mice model of Alzheimer's disease(AD). Methods The experimental mice were divided into non-tg-control (NTC, n=10), tg-control (TC, n=10), and tg-exercise (TE, n=10), and treadmill exercise was conducted for 12 weeks (15m/min, 60min, 5 times/week). And then, we measured the cognitive function using MWM and the brain cortex was evaluated to determine whether any changes in the oligomer Aβ, apoptotic-related factors, mitophagy and mitochondrial biogenesis. Results As a result, treadmill exercise significantly reduced oligomer amyloid and also had a positive effect on proteins (PUMA, Bax, Bcl-2) associated with apoptosis. In addition, through the treadmill exercise, PINK-1 decreased, and increased parkin, showing that active inhibition of mitophagy has been partially relaxed. It has been confirmed that the key autophagy markers LC3 and p62 significantly reduce p62 expression in TE group compared to TC group, and that LC3-II/LC3-I ratio tended to decrease, although not significant, increasing the activity of mitophagy. Next, proteins related to mitochondrial biosynthesis (SIRT-1, PGC-1α, Tfam, and COX-IV) have been identified, and the treadmill exercise has confirmed that the expression of all proteins has increased in part. Finally, cognitive has been shown to improve cognitive by shortening both swimming distance and time through treadmill exercise. Conclusions Thus, our finding suggested treadmill exercise alleviates cognitive dysfunction by improving mitochondrial quality control(mitophagy, mitochondrial biogenesis) and neuronal cell death via reducing amyloid accumulation, which may play a role in a preventive strategy for AD.
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