Physical exercise ameliorates cognitive impairment caused by sleep deprivation by modulating autophagy

Guo Shan, Tang Ling

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Journal of Chongqing Medical University ›› 2025, Vol. 50 ›› Issue (02) : 260-266. DOI: 10.13406/j.cnki.cyxb.003705
Basic research

Physical exercise ameliorates cognitive impairment caused by sleep deprivation by modulating autophagy

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Abstract

Objective Neuronal necrosis resulting from autophagy dysregulation is a key mechanism of cognitive decline caused by sleep disorders. Physical exercise is an effective method to improve cognitive function，but the related mechanism remains to be investigated. The objective of this study was to explore the regulatory effect of physical exercise on autophagy abnormalities associated with sleep disorders. Methods C57BL/6 male mice were randomly divided into a control group，an exercise（EX） group，a sleep deprivation （SD） group，and an exercise intervention（EX+SD） group. Sleep deprivation was used to simulate sleep disorders. Morris water maze was used to evaluate the cognitive function of mice. Hematoxylin-eosin staining and transmission electron microscopy were used to evaluate the degree of hippocampal neuronal injury. Western blotting was adopted to measure the expression of autophagy-related proteins. Results Compared with the control group，sleep deprivation significantly extended the time of searching for the hidden platform （P=0.000） and reduced the time of staying in the target quadrant（P=0.000）. The morphological analysis revealed that neurons in CA3 region of the hippocampus of sleep-deprived mice showed degeneration and karyopyknosis（P=0.000），while autophagosomes increased in the neuron ultrastructure （P=0.000）. Western blotting showed that Beclin-1（P=0.000），LC3（microtubule-associated protein light chain 3，MAPLC3）Ⅱ（P=0.000），and p62（P=0.000） levels were significantly increased in the hippocampus of sleep-deprived mice. However，physical exercise inhibited the up-regulation of Beclin-1（P=0.01），LC3Ⅱ（P=0.018），and p62（P=0.036） induced by sleep deprivation，reduced the number of autophagosomes in neurons（P=0.001），alleviated the morphological injury of neurons（P=0.002），and improved the cognitive behavioral abnormalities of experimental mice. Conclusion The results of this study indicate that sleep deprivation can induce autophagy initiation，but the autophagy flux is blocked，which may be an important pathological link leading to neuronal injury and cognitive impairment. Exercise can promote the patency of autophagy flux and reduce neuronal injury and cognitive impairment.

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sleep disorder / sleep deprivation / physical exercise / cognitive function / autophagy

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Guo Shan , Tang Ling. Physical exercise ameliorates cognitive impairment caused by sleep deprivation by modulating autophagy. Journal of Chongqing Medical University. 2025, 50(02): 260-266 https://doi.org/10.13406/j.cnki.cyxb.003705

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