Lee Jae Min, Sung Da-Eun, Choi You Jung, Yeo Seung Geun, Kim Youn-Jung
Department of Basic Nursing Science, College of Nursing Science, Kyung Hee University, Seoul, Korea.
Department of Otorhinolaryngology Head & Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Seoul, Korea.
Int Neurourol J. 2025 Jul;29(Suppl 1):S13-S21. doi: 10.5213/inj.2550118.059. Epub 2025 Jul 31.
Aging is associated with various physiological changes. These include microvascular dysfunction, which impairs cerebral blood flow and neuronal health, leading to cognitive impairment. Although exercise has demonstrated beneficial effects on aging, its specific impact on age-related microvascular dysfunction and blood-brain barrier (BBB) disruption requires further investigation. This study aimed to evaluate whether an 8-week treadmill exercise regimen in aged mice could improve cognitive impairment by alleviating microvascular and BBB damage and reducing neuroinflammation.
Twenty-month-old C57BL/6J male mice engaged in a treadmill exercise program for 60 minutes daily over 8 weeks. Cognitive function was assessed using the passive avoidance test. Microvascular integrity was evaluated by measuring microvessel length and fragmentation in the cortex using platelet endothelial cell adhesion molecule-1 as a marker. Activation of microglia and astrocytes was determined by analyzing the expression of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein through immunohistochemistry and immunofluorescence. BBB integrity was assessed by examining the expression levels of tight junction proteins, including zonula occludens-1, occludin, claudin-9, and platelet-derived growth factor receptor beta (PDGFRβ), in the cortex via immunostaining and western blotting.
Treadmill exercise significantly improved cognitive function, as indicated by increased latency time in the passive avoidance test. Exercise intervention also increased microvessel length and decreased microvessel fragmentation in the cortex. Additionally, treadmill exercise reduced the activation of microglia and astrocytes, thereby decreasing neuroinflammatory responses. Furthermore, treadmill exercise preserved BBB integrity by maintaining the expression of tight junction proteins and PDGFRβ, counteracting age-related declines.
The findings suggest that regular treadmill exercise mitigates cognitive impairment and vascular dysfunction associated with aging by improving microvascular health and BBB integrity. These results highlight the potential of exercise intervention as a non-pharmacological strategy for treating age-related neurodegenerative diseases by preserving vascular and BBB structures and reducing neuroinflammation.
衰老与多种生理变化相关。这些变化包括微血管功能障碍，其会损害脑血流量和神经元健康，进而导致认知障碍。尽管运动已被证明对衰老有益，但其对与年龄相关的微血管功能障碍和血脑屏障（BBB）破坏的具体影响仍需进一步研究。本研究旨在评估在老年小鼠中进行为期8周的跑步机运动方案是否可以通过减轻微血管和血脑屏障损伤以及减少神经炎症来改善认知障碍。
20月龄的C57BL/6J雄性小鼠进行为期8周的跑步机运动方案，每天运动60分钟。使用被动回避试验评估认知功能。以血小板内皮细胞黏附分子-1为标志物，通过测量皮质中的微血管长度和碎片化程度来评估微血管完整性。通过免疫组织化学和免疫荧光分析离子钙结合衔接分子1和胶质纤维酸性蛋白的表达，以确定小胶质细胞和星形胶质细胞的激活情况。通过免疫染色和蛋白质印迹法检测皮质中紧密连接蛋白（包括闭合蛋白-1、闭锁蛋白、claudin-9和血小板衍生生长因子受体β（PDGFRβ））的表达水平，评估血脑屏障的完整性。
跑步机运动显著改善了认知功能，被动回避试验中的潜伏期延长表明了这一点。运动干预还增加了皮质中的微血管长度并减少了微血管碎片化。此外，跑步机运动减少了小胶质细胞和星形胶质细胞的激活，从而降低了神经炎症反应。此外，跑步机运动通过维持紧密连接蛋白和PDGFRβ的表达来保持血脑屏障的完整性，抵消了与年龄相关的下降。
研究结果表明，定期的跑步机运动通过改善微血管健康和血脑屏障完整性，减轻了与衰老相关的认知障碍和血管功能障碍。这些结果凸显了运动干预作为一种非药物策略的潜力，通过保护血管和血脑屏障结构以及减少神经炎症来治疗与年龄相关的神经退行性疾病。
