Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (5): 1445-1454.doi: 10.4103/NRR.NRR-D-23-01101

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Meifeng Zheng1, 2, 3, # , Borui Zhang3, # , Sonata S Y Yau4 , Kwok-Fai So3, 5, 6, 7 , Li Zhang3, 6, 7, * , Haining Ou1, 2, *   

  1. 1 Department of Rehabilitatton Medicine, Guangzhou Medical University, Guangzhou, Guangdong Province, China;  2 Department of Rehabilitatton Medicine, The Fiffh Clinical College of Guangzhou Medical University, Guangzhou, Guangdong Province, China;  3 Key Laboratory of CNS Regeneratton (Ministry of Educatton), Guangdong-Hong Kong-Macau Instttute of CNS Regeneratton, Jinan University, Guangzhou, Guangdong Province, China;  4 Department of Rehabilitatton Sciences, The Hong Kong Polytechnic University, Hong Kong Special Administrattve Region, China;  5 State Key Laboratory of Brain and Cognittve Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrattve Region, China;  6 Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai, China;  7 Neuroscience and Neurorehabilitatton Instttute, University of Health and Rehabilitatton Sciences, Qingdao, Shandong Province, China
  • Online:2025-05-15 Published:2024-10-31
  • Contact: Li Zhang, PhD, zhangli@jnu.edu.cn; Haining Ou, MD, ouhaining@gzhmu.edu.cn.
  • Supported by:
    This study was supported by STI2030-Major Projects, No. 2022ZD0207600 (to LZ); the Nattonal Natural Science Foundatton of China, Nos. 32070955 (to LZ), U22A20301 (to KFS); the Natural Science Foundatton of Guangdong Province, No. 2021A1515012197 (to HO); Guangzhou Core Medical Disciplines Project, No. 2021-2023 (to HO); Key Research and Development Plan of Ningxia Hui Automomous Region, No. 2022BEG01004 (to KFS); Science and Technology Program of Guangzhou, China, No. 202007030012 (to KFS and LZ).

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Abstract:

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia. We also examined the role of exercise-induced circulating factors in these effects. Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion. We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area, inhibited gliogenesis, protected synaptic proteins, and improved novel object and spatial memory function. Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise. Agonist activation of adiponectin receptors by AdipoRon mimicked the effects of exercise, while inhibiting receptor activation abolished the exercise effects. In summary, our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Key words:

adiponectin, cerebral ischemia, exercise pre-conditioning, hippocampus, memory function, middle cerebral artery occlusion, prefrontal cortex, synaptic proteins, treadmill exercise