Physical Exercise Ameliorates the Cognitive Function and Attenuates the Neuroinflammation of Alzheimer’s Disease via miR-129–5p

Abstract

Introduction: Physical exercise has a significant neuroprotective role in Alzheimer’s disease (AD), but the underlying mechanisms remain elusive. Objective: This study aimed to explore the molecular mechanisms of physical exercise by analyzing the role of microRNA-129–5p (miR-129–5p) in AD mice and patients. Methods: AD mice and patients were treated with 4-week and 3-month physical exercise, respectively. The expression of miR-129–5p was measured using quantitative real-time PCR. The Morris water-maze test was used for cognition evaluation, and enzyme-linked immunosorbent assay was used for inflammation analysis. Results: In both AD mice and patients, the expression of miR-129–5p was elevated by physical exercise. By in vivoregulation of miR-129–5p, we found that the improved cognitive function and reduced inflammatory responses were reversed by the knockdown of miR-129–5p. In patients with AD, the serum expression of miR-129–5p was further found to be correlated with the serum levels of cognitive function markers and proinflammatory cytokines. Conclusion: All data indicated that the expression of miR-129–5p in AD mice and patients is significantly upregulated by physical exercise. The knockdown of miR-129–5p can abrogate the neuroprotective effect of exercise on cognition and neuroinflammation in AD mice. This study provides a novel insight into the molecular mechanisms underlying the neuroprotective effect of physical exercise in AD, and miR-129–5p may provide a novel therapeutic target for AD treatment.