Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.

中文翻译：

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敲低lncRNA TUG1抑制海马神经元凋亡，并参与有氧运动减轻的血管性认知障碍

我们先前的研究表明，有氧运动可通过调节脑源性神经营养因子（BDNF）减轻血管性认知障碍（VCI）患者的认知障碍，但其机制尚不清楚。这项研究旨在探讨lncRNA牛磺酸上调基因1（TUG1）是否通过调节BDNF参与VCI的过程。检测VCI患者血清中TUG1和BDNF的表达。在氧气和葡萄糖剥夺诱导（OGD诱导）海马细胞系HT22中探索了TUG1调节海马神经元凋亡的潜在分子机制。建立了VCI小鼠模型，并通过慢病毒注射过表达TUG1和BDNF。有氧运动后，通过莫里斯水迷宫实验检测小鼠的认知障碍。与对照组相比，VCI患者血清中的TUG1水平升高。OUG诱导的HT22细胞中TUG1的敲低增加了BDNF水平并降低了细胞凋亡，而BDNF的下调则恢复了降低的细胞凋亡。RNA免疫沉淀和RNA下拉检测表明TUG1可以结合BDNF蛋白。有氧运动可减轻VCI小鼠的认知障碍并抑制海马细胞凋亡。同时，TUG1的过表达逆转了有氧运动对认知障碍的治疗作用。敲低TUG1减少海马神经元凋亡，并参与有氧运动减轻的VCI，这部分是通过调节BDNF来实现的。OUG诱导的HT22细胞中TUG1的敲低增加了BDNF的水平并减少了细胞凋亡，而BDNF的下调恢复了减少的细胞凋亡。RNA免疫沉淀和RNA下拉检测表明TUG1可以结合BDNF蛋白。有氧运动可减轻VCI小鼠的认知障碍并抑制海马细胞凋亡。同时，TUG1的过表达逆转了有氧运动对认知障碍的治疗作用。敲低TUG1减少海马神经元凋亡，并参与有氧运动减轻的VCI，这部分是通过调节BDNF来实现的。OUG诱导的HT22细胞中TUG1的敲低增加了BDNF的水平并减少了细胞凋亡，而BDNF的下调恢复了减少的细胞凋亡。RNA免疫沉淀和RNA下拉检测表明TUG1可以结合BDNF蛋白。有氧运动可减轻VCI小鼠的认知障碍并抑制海马细胞凋亡。同时，TUG1的过表达逆转了有氧运动对认知障碍的治疗作用。敲低TUG1减少海马神经元凋亡，并参与有氧运动减轻的VCI，这部分是通过调节BDNF来实现的。有氧运动可减轻VCI小鼠的认知障碍并抑制海马细胞凋亡。同时，TUG1的过表达逆转了有氧运动对认知障碍的治疗作用。敲低TUG1减少海马神经元凋亡，并参与有氧运动减轻的VCI，这部分是通过调节BDNF来实现的。有氧运动可减轻VCI小鼠的认知障碍并抑制海马细胞凋亡。同时，TUG1的过表达逆转了有氧运动对认知障碍的治疗作用。敲低TUG1减少海马神经元凋亡，并参与有氧运动减轻的VCI，这部分是通过调节BDNF来实现的。