Treadmill Exercise Alleviates Neuroinflammation, Demyelination, and Apoptosis Induced by Hyperactivation of Microglia in the Hippocampus of Senescent Mice by Regulating the SIRT1/PPARγ Pathway.

Abstract

Cognitive dysfunction is a major feature of brain aging. However, there is no effective treatment for brain aging. Aerobic exercise is a non-side-effective intervention that is effective in neurodegenerative diseases such as aging. The aim of this study was to explore the potential of treadmill exercise in preventing oxidative stress-induced brain aging and neurodegenerative diseases by investigating the effects of treadmill exercise and its mechanisms in D-galactose-induced mice. The results showed that D-galactose-induced C57BL/6 mice exhibited cognitive deficits, myelin deficits, and increased neuronal apoptosis. Additionally, we observed significantly elevated average optical density values of IBA-1, a microglia-specific marker, in the senescent group. These were effectively mitigated following the treadmill exercise. The study also found that treadmill exercise increased the expression of Silent Information Regulator 1 (SIRT1) and Peroxisome proliferator-activated receptor γ (PPARγ) proteins, while decreasing the expression of p-NFKB. Immunofluorescence double-labeling further validated that SIRT1 and PPARγ co-localized and that treadmill exercise contributed to increased SIRT1 and PPARγ overlapping fluorescence intensity. Treadmill exercise decreased the expression of IL-1β and iNOS, and decreased the number of TUNEL-positive cells and the expression of the apoptosis executor caspase3. The results suggest that aerobic exercise has the potential to ameliorate the cognitive deficits observed in D-galactose mice by modulating the SIRT1/PPARγ signaling pathway to impede microglia-induced neuroinflammation and reduce apoptosis. Treadmill exercise appears to have the potential to be an effective treatment for attenuating microglia inflammation-induced brain aging and neurodegenerative diseases.