Aerobic Exercise Ameliorates Neuroinflammation in AD Mice by Weakening Blood-Brain Barrier Disruption and Microglial Immune Activation
10.13865/j.cnki.cjbmb.2025.08.10093
- VernacularTitle:有氧运动弱化脑漏-小胶质细胞免疫激活改善AD小鼠脑神经炎症
- Author:
Shun-Ling YUAN
1
;
Sheng-Yu DAI
;
Wei LIN
;
Di-Qun XU
;
Yi-Ping LIU
Author Information
1. 福建师范大学体育科学学院,运动与健康福建省高校重点实验室,福州 350117;首都体育学院运动科学与健康学院,北京 100191
- Publication Type:Journal Article
- Keywords:
aerobic exercise;
Alzheimer's disease(AD);
brain leakage;
neuroinflammation
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(11):1700-1710
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the effects of aerobic exercise on neuroinflammation in AD mice and explore the mechanisms of neuroinflammation regulated by the blood-brain barrier,lipopolysaccharide(LPS)displacement,and glial cell activation.Twenty 3-month-old male APP/PS1 double transgenic mice were used,which were randomly divided into a sedentary group(SE-AD)and an aerobic exercise group(Run-AD),and 10 3-month-old male C57BL/6 mice were used as the control group(WT).The Run-AD group underwent 12 weeks of aerobic training.The results of the water maze showed that aerobic exercise improved the learning and memory capacity of AD mice(P<0.05).The results of H&E stai-ning and Nissl staining showed that aerobic exercise reduced necrotic cells and inflammatory cell infiltra-tion in the cerebral cortex,as well as nuclear condensation in the CA1 and GD regions of the hippocam-pus(P<0.05,P<0.01),and increased the area of Nissl bodies in the cerebral cortex and hippocam-pal CA3 and DG regions.Western blotting and ELISA results showed that aerobic exercise increased the expression of Occludin,ZO-1 and Claudin-5 proteins in the brain(P<0.01),and decreased the levels of LPS in the brain(P<0.01).The qRT-PCR results exhibited that aerobic exercise decreased the ex-pression of TLR4,MyD88,NF-κB,IL-1β,and TNF-α mRNA(P<0.05,P<0.01).The results of immunofluorescence staining revealed that aerobic exercise reduced the fluorescence area of brain IL-1βand TNF-α proteins(P<0.05,P<0.01),as well as the fluorescence area of Iba-1,GFAP,and TLR4 proteins in the cerebral cortex and hippocampus(P<0.05,P<0.01).There was a high degree of overlap between Iba-1 and TLR4 fluorescence in the cerebral cortex,and GFAP was localized around Iba-1.In summary,aerobic exercise attenuates neuroinflammation in AD mice by protecting the blood-brain barrier,reducing the displacement of LPS,and subsequently weakening the immune activation of microglia to regulate the TLR4/MyD88/NF-κB signaling pathway to alleviate neuroinflammation.