Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (3): 657-662.doi: 10.4103/1673-5374.377771

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Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Hang Yu1, #, Mingting Shao1, #, Xi Luo1, Chaoqin Pang1, Kwok-Fai So1, 2, 3, *, Jiandong Yu1, 4, *, Li Zhang1, 3, 5, *   

  1. 1Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China; 2State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; 3Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province, China; 4Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Shandong Province, China; 5School of Psychology, Shanghai University of Sport, Shanghai, China
  • Online:2024-03-15 Published:2023-09-02
  • Contact: Kwok-Fai So, PhD, hrmaskf@hku.hk; Jiandong Yu, PhD, jiandongyu@qq.com; Li Zhang, PhD, zhangli@jnu.edu.cn.
  • Supported by:
    This study was supported by STI2030-Major Projects, No. 2022ZD0207600 (to LZ), the National Natural Science Foundation of China, Nos. 82171446 (to JY), U22A20301 (to KFS), 32070955 (to LZ), Guangdong Basic and Applied Basic Research Foundation, No. 2023B1515040015 (to LZ), and Science and Technology Program of Guangzhou of China, No. 202007030012 (to KFS and LZ).

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Abstract: Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited. Although regular exercise effectively improves learning and memory functions across multiple neurological diseases, its application in patients with epilepsy remains controversial. Here, we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy. Cognitive assays confirmed the improvement of object and spatial memory after endurance training, and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise. Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons, probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier. In summary, this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Key words: blood-brain barrier, cognition, hippocampus, interneurons, long-term potentiation, microglial cell, neuroinflammation, spatial memory, temporal epilepsy, treadmill exercise