中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3641-3649.doi: 10.4103/NRR.NRR-D-24-00463

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

 5-羟色胺3受体在有氧运动诱导的记忆改善和海马突触可塑性中的作用

  

  • 出版日期:2026-08-18 发布日期:2026-04-27
  • 基金资助:
    该研究受到国家自然科学基金面上项目(31972914, 31771175)资助

Role of 5-hydroxytryptamine type 3 receptors in aerobic exercise–induced improvement of memory and hippocampal synaptic plasticity

Xiaoqian He1, #, Ziying Lai1, #, Xueyan Wang1, Jingjing Li1, Guangbing Duan2, Junwen Wang2, Zhao Qin1, Shuchang Xu2, Ying Huang1, *   

  1. 1Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Ministry of Education), Department of Physiology and Pharmacology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China; 
    2Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Ying Huang, PhD, yinghuang@tongji.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 31972914, 31771175 (both to YH).

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摘要：

有氧运动可促进突触可塑性，从而改善学习和记忆等认知功能。既往研究表明5-羟色胺3受体在运动改善认知记忆中具有重要作用，但关于5-羟色胺3受体在有氧运动促进海马突触可塑性的作用及机制研究仍不清晰。实验发现，5-羟色胺3受体在跑步机有氧运动改善小鼠海马依赖性空间和探索记忆中发挥了重要作用。虽然5-羟色胺3受体不影响海马齿状回的基线神经发生，但有氧运动诱导的神经发生和星形胶质细胞增殖需要5-羟色胺3受体的参与。此外，5-羟色胺3受体对维持海马 CA1、齿状回 和 CA3 区的长时程增强至关重要。有趣的是，在有氧运动增强海马CA3区的长时程增强过程中，5-羟色胺3受体是必不可少的，但在CA1区和齿状回则不然。此外，有氧运动上调了5-羟色胺3受体表达，并以5-羟色胺3受体依赖的方式增加了小鼠海马中脑源性神经营养因子的释放。这些结果表明，有氧运动通过上调5-羟色胺3受体增加了海马齿状回的神经发生和星形胶质细胞的增殖，导致这些细胞产生和释放更多的脑源性神经营养因子，从而促进了海马CA3区的长时程增强，有助于改善记忆功能。实验提供了5-羟色胺3受体在有氧运动改善记忆功能中的关键作用的证据。考虑到有氧运动对神经退行性疾病的有益作用，5-羟色胺3受体可能成为治疗此类疾病的潜在靶点。


https://orcid.org/0000-0001-7002-8197 (Ying Huang)

关键词: 5-羟色胺3受体, 有氧运动, 空间记忆, 探索性记忆, 海马, 神经发生, 神经胶质细胞增殖, 脑源性神经营养因子, 长时程增强, 5-羟色胺

Abstract: Aerobic exercise facilitates synaptic plasticity, thereby improving cognitive functions such as learning and memory. The 5-hydroxytryptamine system has been indicated in these processes. 5-Hydroxytryptamine type 3 receptors are necessary for exercise-induced hippocampal neurogenesis. Some antipsychotic drugs with 5-hydroxytryptamine type 3 receptor antagonistic properties may impede the amelioration of cognitive impairment and hippocampal plasticity induced by exercise. However, the mechanisms underlying the facilitation of synaptic plasticity by aerobic exercise have not yet been elucidated. In this study, we found that 5-hydroxytryptamine type 3 receptors played an important role in aerobic exercise–mediated improvement of hippocampal-dependent spatial and exploratory memory in mice. While 5-hydroxytryptamine type 3 receptors did not affect baseline neurogenesis in the hippocampal dentate gyrus, 5-hydroxytryptamine type 3 receptors were required for aerobic exercise–induced neurogenesis and astrocyte proliferation in this region. In addition, 5-hydroxytryptamine type 3 receptors were crucial for maintaining long-term potentiation in the CA1, dentate gyrus, and CA3 regions of the hippocampus. The long-term potentiation changes induced by aerobic exercise in sub-regions of the hippocampus were heterogeneous: 5-hydroxytryptamine type 3 receptors were essential for aerobic exercise to enhance long-term potentiation in the CA3, but not the CA1 or dentate gyrus, regions of the hippocampus. Furthermore, aerobic exercise up-regulated 5-hydroxytryptamine type 3 receptor expression and increased brain-derived neurotrophic factor release in the hippocampus in a 5-hydroxytryptamine type 3 receptor–dependent manner. These results suggest that aerobic exercise increases hippocampal dentate gyrus neurogenesis and astrocyte proliferation via the up-regulation of 5-hydroxytryptamine type 3 receptors, leading to more brain-derived neurotrophic factor production and release from these cells, which results in long-term potentiation facilitation in the hippocampal CA3 region and help improve memory. Our findings provide insight into the mechanisms by which physical activity enhances memory and may have implications for improving memory through modulating 5-hydroxytryptamine type 3 receptor.


Key words: 5-hydroxytryptamine, 5-hydroxytryptamine type 3 receptor, aerobic exercise, brain-derived neurotrophic factor, exploratory memory, hippocampus, long-term potentiation, neurogenesis, neuroglia proliferation, spatial memory