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

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.