ORIGINAL RESEARCH article

Front. Physiol.

Sec. Integrative Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1608268

Aerobic exercise ameliorates atherosclerosis-induced cognitive impairment via hippocampal IL-33/NF-κB signaling modulation

Provisionally accepted
Jianwei  PengJianwei Peng1Zaoshang  ChangZaoshang Chang2Jinyun  WangJinyun Wang1Zijie  LiaoZijie Liao2Yunjie  YangYunjie Yang1Lianwei  MuLianwei Mu1Shen  WangShen Wang1Junhao  HuangJunhao Huang1*Jingbo  XiaJingbo Xia1*Min  HuMin Hu1*
  • 1Guangzhou Sport University, Guangzhou, Guangdong Province, China
  • 2Shaoyang University, Shaoyang, China

The final, formatted version of the article will be published soon.

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.

Keywords: aerobic exercise, Atherosclerosis, cognitive impairment, IL-33 signaling, inflammatory cytokines

Received: 08 Apr 2025; Accepted: 29 May 2025.

Copyright: © 2025 Peng, Chang, Wang, Liao, Yang, Mu, Wang, Huang, Xia and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Junhao Huang, Guangzhou Sport University, Guangzhou, 510500, Guangdong Province, China
Jingbo Xia, Guangzhou Sport University, Guangzhou, 510500, Guangdong Province, China
Min Hu, Guangzhou Sport University, Guangzhou, 510500, Guangdong Province, China

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