Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600, Tianhe Road, Guangzhou, 510630, China.
Neurochem Res. 2021 Jun;46(6):1540-1553. doi: 10.1007/s11064-021-03294-1. Epub 2021 Mar 11.
Physical exercise is beneficial to the structural and functional recovery of post-ischemic stroke, but its molecular mechanism remains obscure. Herein, we aimed to explore the underlying mechanism of exercise-induced neuroprotection from the perspective of microRNAs (miRNAs). Adult male Sprague-Dawley (SD) rats were randomly distributed into 4 groups, i.e., the physical exercise group with the transient middle cerebral artery occlusion (tMCAO) surgery (PE-IS, n = 28); the physical exercise group without tMCAO surgery (PE, n = 6); the sedentary group with tMCAO surgery (Sed-IS, n = 28); and the sedentary group without tMCAO surgery (Sed, n = 6). Notably, rats in the PE-IS and PE groups were subjected to a running exercise for 28 days while rats in the Sed-IS and Sed groups received no exercise training. After long-term exercise, exosomal miRNAs of cerebrospinal fluid (CSF) were analyzed using high-throughput sequencing. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed for the differentially expressed miRNAs. Physical exercise improved the neurological function and attenuated the lesion expansion after stroke. In total, 41 differentially expressed miRNAs were screened for the GO and KEGG analysis. GO enriched terms were associated with the central nervous system, including cellular response to retinoic acid, vagus nerve morphogenesis, cellular response to hypoxia, dendritic cell chemotaxis, cell differentiation, and regulation of neuron death. Besides, these differentially expressed miRNAs were linked to the pathophysiological process of stroke, including axon guidance, NF-kappa B signaling pathway, thiamine metabolism, and MAPK signaling pathway according to KEGG analysis. In summary, exercise training significantly alleviated the neurological damage at both functional and structural levels. Moreover, the differentially expressed miRNAs regulating multiple signal pathways were potentially involved in the neuroprotective effects of physical exercise. Therefore, these miRNAs altered by physical exercise might represent the therapeutic strategy for cerebral ischemia.
体育锻炼有益于缺血性中风后的结构和功能恢复，但其中的分子机制尚不清楚。在此，我们旨在从 microRNAs (miRNAs) 的角度探讨运动诱导的神经保护的潜在机制。成年雄性 Sprague-Dawley (SD) 大鼠随机分为 4 组，即伴有短暂性大脑中动脉闭塞 (tMCAO) 手术的运动组 (PE-IS，n = 28)；无 tMCAO 手术的运动组 (PE，n = 6)；伴有 tMCAO 手术的安静组 (Sed-IS，n = 28)；和无 tMCAO 手术的安静组 (Sed，n = 6)。值得注意的是，PE-IS 和 PE 组的大鼠进行了 28 天的跑步运动，而 Sed-IS 和 Sed 组的大鼠则没有进行运动训练。经过长期运动后，使用高通量测序分析脑脊液 (CSF) 的外泌体 miRNAs。此外，对差异表达的 miRNAs 进行了基因本体 (GO) 和京都基因与基因组百科全书 (KEGG) 分析。运动锻炼改善了中风后的神经功能和损伤扩大。总共筛选出 41 个差异表达的 miRNA 进行 GO 和 KEGG 分析。GO 富集术语与中枢神经系统有关，包括对维甲酸的细胞反应、迷走神经形态发生、缺氧的细胞反应、树突状细胞趋化性、细胞分化和神经元死亡的调节。此外，根据 KEGG 分析，这些差异表达的 miRNAs 与中风的病理生理过程有关，包括轴突导向、NF-kappa B 信号通路、硫胺素代谢和 MAPK 信号通路。总之，运动训练显著减轻了功能和结构水平的神经损伤。此外，调节多种信号通路的差异表达 miRNAs 可能参与了运动的神经保护作用。因此，运动改变的这些 miRNA 可能代表了脑缺血的治疗策略。
