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Bioinformatic Analysis of Exosomal MicroRNAs of Cerebrospinal Fluid in Ischemic Stroke Rats After Physical Exercise

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Abstract

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.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81972151, 81572228) and the Guangdong Basic and Applied Basic Research Foundation (2019A1515011106).

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  1. Mudan Huang and Chongjun Xiao contributed equally to this study.

Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600, Tianhe Road, Guangzhou, 510630, China

    Mudan Huang, Chongjun Xiao, Liying Zhang, Lili Li, Jing Luo, Lilin Chen, Xiquan Hu & Haiqing Zheng

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Contributions

MH and CX are joint first authors. MH, CX and LZ carried out the assays. LL, JL and LC assisted with the experiments. MH and CX performed the data analysis and wrote the paper. XH and HZ participated in the design of the study. HZ conceived the research study and contributed to draft the manuscript.

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Correspondence to Haiqing Zheng.

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All experimental procedures of this study were approved by the Institutional Animal Ethical Committee of Sun Yat-sen University and conducted following the Guide for the Care and Use of Laboratory Animal of the National Institute of Health.

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Huang, M., Xiao, C., Zhang, L. et al. Bioinformatic Analysis of Exosomal MicroRNAs of Cerebrospinal Fluid in Ischemic Stroke Rats After Physical Exercise. Neurochem Res 46, 1540–1553 (2021). https://doi.org/10.1007/s11064-021-03294-1

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