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Moderate-Intensity Intermittent Training Inhibits miR-34a-5p to Reduce Prefrontal Cortex Apoptosis and Improve Cognitive Ability in Aging Rats Reduced by D-galactose

Gao, Q.; Zhang, J.; Lv, L.; Gao, J.; Li, M.; Li, X.; Wang, L.

2025-08-23 physiology
10.1101/2025.08.19.671180 bioRxiv
Show abstract

Changes in microRNA (miRNA) play a role in brain aging. They are considered potential therapeutic targets. Regular long-term exercise benefits brain health. However, its exact mechanism is not fully understood. This study explored how moderate-intensity intermittent training (MIIT) improves cognitive function and reduces apoptosis in the aging brain. This study induced aging in rats by giving them D-gal injections (150 mg/kg/day) for 6 weeks. After confirming the model, the rats underwent MIIT. They exercised 45 minutes a day, 5 days a week, for 8 weeks. The results from behavioral, morphological, and molecular tests showed that 8 weeks of MIIT significantly slowed the decline in spatial learning and memory in D-gal aging rats. The exercise also improved the structure of the prefrontal cortex (PFC) and reduced apoptosis. Aging caused an overexpression of miR-34a-5p in the prefrontal cortex. MIIT reduced this overexpression. It also up-regulated Notch1 and inhibited excessive apoptosis by regulating Bcl-2 and Bax expression. In conclusion, MIIT may improve brain health by targeting miR-34a-5p and regulating apoptosis-related pathways.

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