Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice
Purpose 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 microvas...
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Korean Continence Society
2025-07-01
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| Series: | International Neurourology Journal |
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| Online Access: | http://einj.org/upload/pdf/inj-2550118-059.pdf |
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| author | Jae Min Lee Da-Eun Sung You Jung Choi Seung Geun Yeo Youn-Jung Kim |
| author_facet | Jae Min Lee Da-Eun Sung You Jung Choi Seung Geun Yeo Youn-Jung Kim |
| author_sort | Jae Min Lee |
| collection | DOAJ |
| description | Purpose 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. Methods 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. Results 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. Conclusions 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. |
| format | Article |
| id | doaj-art-79437a275cf34774b4093e76b37f2d70 |
| institution | DOAJ |
| issn | 2093-4777 2093-6931 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Continence Society |
| record_format | Article |
| series | International Neurourology Journal |
| spelling | doaj-art-79437a275cf34774b4093e76b37f2d702025-08-20T02:48:53ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312025-07-0129Suppl 1S13S2110.5213/inj.2550118.0591167Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in MiceJae Min Lee0Da-Eun Sung1You Jung Choi2Seung Geun Yeo3Youn-Jung Kim4 Department of Basic Nursing Science, College of Nursing Science, Kyung Hee University, Seoul, Korea Department of Nursing, Graduate School, Kyung Hee University, Seoul, Korea Department of Nursing, Graduate School, Kyung Hee University, Seoul, Korea Department of Otorhinolaryngology Head & Neck Surgery, College of Medicine, Kyung Hee University Medical Center, Seoul, Korea Department of Basic Nursing Science, College of Nursing Science, Kyung Hee University, Seoul, KoreaPurpose 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. Methods 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. Results 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. Conclusions 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.http://einj.org/upload/pdf/inj-2550118-059.pdfagingcognitive impairmenttreadmill exercisebood-brain barrierneuroinflammation |
| spellingShingle | Jae Min Lee Da-Eun Sung You Jung Choi Seung Geun Yeo Youn-Jung Kim Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice International Neurourology Journal aging cognitive impairment treadmill exercise bood-brain barrier neuroinflammation |
| title | Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice |
| title_full | Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice |
| title_fullStr | Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice |
| title_full_unstemmed | Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice |
| title_short | Neurovascular Restoration by Treadmill Exercise Attenuates Age-Related Cognitive Decline in Mice |
| title_sort | neurovascular restoration by treadmill exercise attenuates age related cognitive decline in mice |
| topic | aging cognitive impairment treadmill exercise bood-brain barrier neuroinflammation |
| url | http://einj.org/upload/pdf/inj-2550118-059.pdf |
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