Exercise Training Mitigated Aortic Dysfunction In Mice With Alzheimer's Disease: Its Underlying Mechanisms

Emerging evidence has seen cerebrovascular pathology as the primary trigger for Alzheimer's disease (AD). Cerebrovascular dysfunction and amyloid-beta (Aβ) deposition are associated with stiffened aorta in AD. Thus, restoring aortic function could be a fundamental solution for the treatment and prevention of AD. However, the protective effects of exercise training (EX) on aortic dysfunction and its underlying mechanisms in AD are unknown. PURPOSE: To investigate the underlying mechanisms for the protective effect of EX on AD-induced aortic endothelial dysfunction. METHODS: Control (C57BL/6, CON) and AD (APP/PS1dE9, AD) mice underwent a 12-week treadmill exercise training. The expression of 5-HT1B and P2Y2 receptors, endothelial nitric oxide synthase (eNOS), and protein markers of oxidative stress, inflammation, and endoplasmic reticulum (ER) stress-induced apoptosis in aortas were quantified by Western blot analysis. RESULTS: EX reduced the expression of 5-HT1B receptors and increased the expression of P2Y2 receptors and eNOS in AD mice aorta. EX increased the expression of SOD2, UCP2, and APPL1, and reduced the expression of Aβ, TNF-α, and IL-1β in AD mice aorta. EX also improved the expression of aberrant ER stress markers, CHOP and Bcl-2 in AD mice aorta. CONCLUSION: Exercise mitigated AD-induced aortic dysfunction by enhanced eNOS activity, possibly through the improvement of 5-HT1B receptors, P2Y2 receptors, ROS, inflammation, and ER stress-induced apoptosis. This work was supported by University of Houston College of Liberal Arts and Social Science Research Progress Grant and Project Completion Grant, and the American College of Sport Medicine Foundation Doctoral Student Research Grant 17-00587.