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Treadmill Exercise Mitigates Alzheimer's Pathology by Modulating Glial Polarization and Reducing Oligodendrocyte Precursor Cell Perivascular Clustering.
Medicine & Science in Sports & Exercise ( IF 4.1 ) Pub Date : 2025-01-16 , DOI: 10.1249/mss.0000000000003650
Chongyun Wu,Peibin Zou,Ling Zhu,Shu Feng,Qianting Deng,Timon Cheng-Yi Liu,Rui Duan,Luodan Yang
Medicine & Science in Sports & Exercise ( IF 4.1 ) Pub Date : 2025-01-16 , DOI: 10.1249/mss.0000000000003650
Chongyun Wu,Peibin Zou,Ling Zhu,Shu Feng,Qianting Deng,Timon Cheng-Yi Liu,Rui Duan,Luodan Yang
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 (OPCs) in perivascular clustering. Additionally, 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 dependent glial phenotypic changes surrounding amyloid plaques in the AD cortex and hippocampus. Further, immunofluorescence staining revealed that exercise alleviated plaque-associated glial changes in these regions. Exercise also alleviated the reduction of microglial SIRPα and reduced synaptic loss mediated by microglial and astrocyte phagocytosis. Lastly, exercise mitigated OPC senescence and cellular senescence-induced OPC perivascular clustering in AD mice.
CONCLUSIONS
Exercise can counteract AD pathological features by modulating glial responses and reducing OPC senescence and perivascular clustering near amyloid plaques, highlighting its potential as a therapeutic strategy for AD.
中文翻译:
跑步机运动通过调节神经胶质极化和减少少突胶质细胞前体细胞血管周围聚集来减轻阿尔茨海默病的病理。
目的 本研究旨在探讨与淀粉样斑块不同距离的神经胶质细胞的病理反应以及血管周围聚集中少突胶质细胞前体细胞 (OPC) 的特征。此外,它试图探索运动训练对 AD 病理学的影响,特别关注神经胶质反应的调节和 OPC 血管周围聚集的影响。方法 将 3 个月龄 C57BL/6 和 APP/PS1 小鼠分为 4 组:野生型久坐组、野生型运动组、久坐型 AD 组和运动型 AD 组。进行巴恩斯迷宫测试以分析空间学习和记忆。采用酶联免疫吸附测定 (ELISA) 分析、免疫荧光染色、Fluro-Jade C 染色、TUNEL 染色、Sholl 分析和 3D 渲染分析检测 Aβ 1-42、tau 过度磷酸化、典型淀粉样蛋白斑块、异常 tau 磷酸化、神经元损伤、细胞凋亡、神经变性、小胶质细胞和星形胶质细胞活化和表型极化,以及 OPC 血管周围聚集。结果 行为结果显示,长期运动训练改善了 APP/PS1 小鼠的认知缺陷。组织病理学分析显示淀粉样蛋白沉积减少,tau 过度磷酸化减少。免疫荧光和 Fluro-Jade C 染色表明,运动减轻了神经元损伤、变性和细胞凋亡。Sholl 和 3D 渲染分析表明,运动减轻了 AD 皮层和海马体淀粉样蛋白斑块周围的空间依赖性神经胶质表型变化。此外,免疫荧光染色显示运动减轻了这些区域斑块相关的神经胶质变化。 运动还减轻了小胶质细胞 SIRPα 的减少,并减少了由小胶质细胞和星形胶质细胞吞噬作用介导的突触丢失。最后,运动减轻了 AD 小鼠的 OPC 衰老和细胞衰老诱导的 OPC 血管周围聚集。结论 运动可以通过调节神经胶质反应和减少 OPC 衰老和淀粉样蛋白斑块附近的血管周围聚集来抵消 AD 病理特征,突出了其作为 AD 治疗策略的潜力。
更新日期:2025-01-16
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
跑步机运动通过调节神经胶质极化和减少少突胶质细胞前体细胞血管周围聚集来减轻阿尔茨海默病的病理。
目的 本研究旨在探讨与淀粉样斑块不同距离的神经胶质细胞的病理反应以及血管周围聚集中少突胶质细胞前体细胞 (OPC) 的特征。此外,它试图探索运动训练对 AD 病理学的影响,特别关注神经胶质反应的调节和 OPC 血管周围聚集的影响。方法 将 3 个月龄 C57BL/6 和 APP/PS1 小鼠分为 4 组:野生型久坐组、野生型运动组、久坐型 AD 组和运动型 AD 组。进行巴恩斯迷宫测试以分析空间学习和记忆。采用酶联免疫吸附测定 (ELISA) 分析、免疫荧光染色、Fluro-Jade C 染色、TUNEL 染色、Sholl 分析和 3D 渲染分析检测 Aβ 1-42、tau 过度磷酸化、典型淀粉样蛋白斑块、异常 tau 磷酸化、神经元损伤、细胞凋亡、神经变性、小胶质细胞和星形胶质细胞活化和表型极化,以及 OPC 血管周围聚集。结果 行为结果显示,长期运动训练改善了 APP/PS1 小鼠的认知缺陷。组织病理学分析显示淀粉样蛋白沉积减少,tau 过度磷酸化减少。免疫荧光和 Fluro-Jade C 染色表明,运动减轻了神经元损伤、变性和细胞凋亡。Sholl 和 3D 渲染分析表明,运动减轻了 AD 皮层和海马体淀粉样蛋白斑块周围的空间依赖性神经胶质表型变化。此外,免疫荧光染色显示运动减轻了这些区域斑块相关的神经胶质变化。 运动还减轻了小胶质细胞 SIRPα 的减少,并减少了由小胶质细胞和星形胶质细胞吞噬作用介导的突触丢失。最后,运动减轻了 AD 小鼠的 OPC 衰老和细胞衰老诱导的 OPC 血管周围聚集。结论 运动可以通过调节神经胶质反应和减少 OPC 衰老和淀粉样蛋白斑块附近的血管周围聚集来抵消 AD 病理特征,突出了其作为 AD 治疗策略的潜力。