Treadmill Exercise Mitigates Alzheimer’s Pathology by Modulating Glial Polarization and Reducing Oligodendrocyte Precursor Cell Perivascular Clustering

作者：Chongyun Wu, Peibin Zou, Ling Zhu, Shu Feng, Qianting Deng, Timon Cheng‐Yi Liu, Rui Duan, LUODAN YANG · 发表于：Medicine & Science in Sports & Exercise · 年份：2025 · DOI：10.1249/mss.0000000000003650 · 被引用次数：13 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms

PURPOSE: This study aimed to investigate the pathological responses of glial cells at different distances from amyloid plaques and the characteristics of oligodendrocyte precursor cells (OPC) in perivascular clustering. In addition, it sought to explore the impact of exercise training on AD pathology, specifically focusing on the modulation of glial responses and the effects of OPC perivascular clustering. METHODS: Three-month-old C57BL/6 and APP/PS1 mice were divided into four groups: wild-type sedentary, wild-type exercise, sedentary AD, and exercise AD groups. The Barnes maze test was conducted to analyze spatial learning and memory. Enzyme-linked immunosorbent assay (ELISA) analysis, Immunofluorescence staining, Fluro-Jade C staining, TUNEL staining, Sholl analysis, and 3D rendering analysis were employed to detect Aβ 1-42, tau hyperphosphorylation, typical amyloid plaques, abnormal tau phosphorylation, neuronal damage, apoptosis, neurodegeneration, microglial and astrocytic activation and phenotypic polarization, and OPC perivascular clustering. RESULTS: Behavioral results revealed that long-term exercise training ameliorated cognitive deficits in APP/PS1 mice. Histopathological analysis showed a reduction in amyloid deposition and decreased tau hyperphosphorylation. Immunofluorescence and Fluro-Jade C staining indicated that exercise attenuated neuronal damage, degeneration, and apoptosis. Sholl and 3D rendering analysis demonstrated that exercise mitigated spatially de...