Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus
Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus
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DOI：
10.1016/j.brainres.2020.146710
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发表时间：
2020-04-01
期刊：
影响因子：
2.9
通讯作者：
Masaki, Tsutomu
中科院分区：
文献类型：
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作者：
Takata, Tadayuki;Nonaka, Wakako;Masaki, Tsutomu
以前，我们研究了可能的缺血性运动的神经保护作用在沙土鼠模型的短暂性全脑缺血和评估的组织学，特定蛋白质的表达，和脑功能在不同的条件下。本研究探讨了无乳酸升高的轻度运动对沙土鼠缺血/再灌注损伤的神经保护作用。通过阻断双侧颈总动脉5 min诱导短暂性全脑缺血。一组动物在缺血诱导前进行跑台运动。评估海马神经元损伤和miRNA表达，以及行为缺陷和血浆乳酸水平。轻度运动抑制海马神经元的丢失，并保留短期记忆。此外，14个miRNAs（mmu-miR-211-3p，-327，-451b，-711，-3070-3p，-3070-2-3p，-3097-5p，-3620-5p，-6240，-6916-5p，-6944-5p，7083-5p，-7085-5p，和-7674-5p）上调，6种miRNAs（mmu-miR-148 b-3 p、-152-3p、-181c-5p、-299b-5p、-455-3p和-664-3p）由于缺血而下调。然而，当动物在缺血事件之前进行轻度运动时，这些miRNAs的表达保持不变。差异表达的miRNAs调节多种生物学过程，如炎症、代谢和细胞死亡。这些发现表明，轻度运动通过调节海马miRNA减少短暂缺血后的神经元死亡和行为缺陷。
Previously we studied the possible neuroprotective effects of ischemia-resistant exercise in a gerbil model of transient whole-brain ischemia and evaluated the histology, expression of specific proteins, and brain function under different conditions. The present study investigated the neuroprotective effects of light exercise, without lactate elevation, in a gerbil model of ischemia/reperfusion injury. Transient whole-brain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. A group of animals was subjected to treadmill exercise before ischemia induction. Hippocampal neuronal damage and miRNA expression, as well as behavioral deficits and plasma lactate levels, were evaluated. Light exercise suppressed hippocampal neuron loss and preserved short-term memory. Moreover, 14 miRNAs (mmu-miR-211-3p, -327, -451b, -711, -3070-3p, -3070-2-3p, -3097-5p, -3620-5p, -6240, -6916-5p, -6944-5p, 7083-5p, -7085-5p, and -7674-5p) were upregulated and 6 miRNAs (mmu-miR-148b-3p, -152-3p, -181c-5p, -299b-5p, -455-3p, and -664-3p) were downregulated due to ischemia. However, the expression of these miRNAs remained unchanged when animals performed light exercise before the ischemic event. Differentially expressed miRNAs regulate multiple biological processes such as inflammation, metabolism, and cell death. These findings suggest that light exercise reduces neuronal death and behavioral deficits after transient ischemia by regulating hippocampal miRNAs.