Exercise-Mediated Alteration of miR-192-5p Is Associated with Cognitive Improvement in Alzheimer's Disease

Abstract

Introduction: Physical exercise is an important component of managing Alzheimer's disease (AD). miRNAs can be modulated by exercise intervention.

Objective: The study explored the involvement and potential mechanism of miR-192-5p in the protective effect of physical exercise on AD.

Methods: Ninety AD patients were enrolled, in which 45 cases accepted cycling training for continuous 3 months. The expression changes of miR-192-5p before and after exercise were analyzed by reverse transcription-quantitative PCR. 8-month-old APP/PS1 double Tg mice were used as the AD animal model. Mice in the voluntary exercise (VE) group received VE for 4 weeks. Morris water maze (MWM) test was used to evaluate the learning and memory function. Enzyme-linked immunosorbent assay was used to calculate the level of IL-1β, IL-6, and TNF-α.

Results: AD patients showed elevated MMSE scores, decreased ADAS-cog and NPI-Q scores after 3 months of exercise. miR-192-5p was downregulated in the serum of AD patients and correlated with the levels of MMSE score, ADAS-cog, and NPI-Q score. A positive association was detected between serum miR-192-5p with TNF-α, IL-6, and IL-1β levels. MiR-192-5p is downregulated in the hippocampus tissues of mice after VE. Overexpression of miR-192-5p reversed the neuroprotective effect of exercise on AD in mice and promoted the inflammatory response of AD mice.

Conclusion: MiR-192-5p can be modulated by the exercise intervention and involved in the protective effect of exercise on AD.

Keywords: APP/PS1 mice; Alzheimer’s disease; Exercise; Morris water maze test; miR-192-5p.