Journal Article Epublish
PubMed: 40556958 DOI: 10.3389/fphys.2025.1608268
Aerobic exercise ameliorates atherosclerosis-induced cognitive impairment via hippocampal IL-33/NF-κB signaling modulation.
Front Physiol 16:1608268
Authors: Jianwei Peng, Zaoshang Chang, Jinyun Wang, Zijie Liao, Yunjie Yang, Lianwei Mu, Shen Wang, Junhao Huang, Jingbo Xia, Min Hu
Affiliations
- Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou, China.
- Department of Physiology, Shaoyang University, Shaoyang, China.
Abstract
Atherosclerosis (AS), a common cardiovascular condition, is often linked to cognitive dysfunction. This study investigates how aerobic exercise affects cognitive impairments caused by AS in ApoE -/- mice. At 8 weeks old, male ApoE -/- mice were fed a high-fat, high-cholesterol diet (HFHCD) for 6 weeks to induce AS, with C57BL/6J mice on a standard diet as control group (WT). Initially, the study compared aortic plaque and cognitive performance between the WT and AS mice. Then, AS mice were divided into sedentary (AS-SED) and exercise (AS-EX) groups for a 10-week aerobic exercise intervention. Results showed significant aortic plaques and cognitive deficits in AS mice after 6 weeks on the HFHCD diet. However, the 10-week exercise reduced plaque, improved cognition, and enhanced cerebral blood flow. Exercise intervention also decreased IL-33 expression in the hippocampus and inhibited NF-κB and IκBα phosphorylation. Furthermore, aerobic exercise reduces M1 microglial activation and pro-inflammatory cytokines like IL-6, TNF-α, and IL-1β in the hippocampus of AS mice, thereby decreasing neuroinflammation. In summary, aerobic exercise can effectively improve cognitive function by decreasing IL-33 expression and inhibiting NF-κB activation, which in turn reduces microglial activation and the release of inflammatory mediators in the hippocampus. This study provides evidence for aerobic exercise to improve cognitive impairment caused by AS.
MeSH
Exercise, Hippocampus, Cognitive Dysfunction, Diet, Cognition Disorders, Atherosclerosis, Interleukin-33, Cognition