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MiR-410-3p overexpression ameliorates neurological deficits in rats with hypoxic-ischemic brain damage.
Brain Research Bulletin ( IF 3.8 ) Pub Date : 2020-06-21 , DOI: 10.1016/j.brainresbull.2020.06.011
Qiu-Xia Xiao 1 , Song Wen 1 , Xue-Rong Zhang 2 , Lu-Lu Xue 3 , Zi-Bin Zhang 4 , Ya-Xin Tan 3 , Ruo-Lan Du 4 , Zhao-Qiong Zhu 1 , Yu-Hang Zhu 1 , Ting-Hua Wang 5 , Chang-Yin Yu 1 , Liu-Lin Xiong 6
Affiliation  

Neonatal hypoxic-ischemic encephalopathy (HIE) is major cause of neonatal death or long-term neurodevelopmental disabilities, which becomes a major practical problem currently in clinic. Whereas, its pathophysiology and underlying molecular mechanism is not clear. MicroRNAs are involved in the normal growth and development of neuronal cells. Herein, the objective of this research was to examine the roles of miR-410-3p in neurological deficits, neuronal injury and neuron apoptosis after hypoxic-ischemic and to explore its associated mechanisms. We established the hypoxic-ischemic brain damage (HIBD) model and oxygen glucose deprivation (OGD) model. Zea-longa score and TTC staining were used to detect the acute cerebral dysfunction after HIBD. QPCR verification exhibited notable downregulation of miR-410-3p expression at 24 h in rats after HIBD as well as that in PC12, SY5Y cells and primary cortical neurons post OGD. To further determine the function of miR-410-3p, lentivirus-mediated overexpression virus was applied in vivo and in vitro. Behavioral tests, including Morris water maze, open field test, Y maze test, neurological severity score and rotating rod test, were performed to evaluate long-term behavioral changes of rats at 1 month post HIBD. The results showed that the number of cells together with the axonal length were reduced post OGD. While the increase of cells number and the axonal length was measured after upregulating miR-410-3p. Meanwhile, miR-410-3p overexpression inhibited neuron apoptosis and enhanced neuronal survival. In addition, long-term motor and cognitive functions were remarkably recovered in HIBD rats with miR-410-3p overexpression. Together, miR-410-3p exerts a critical role in protecting neuronal growth as well as promoting motor and cognitive function recovery in neonatal rats subjected to HIBD. The current study therefore provides critical insights to develop the activator of miR-410-3p for the clinical treatment of HIBD in future clinic trial.



中文翻译:

MiR-410-3p 过表达可改善缺氧缺血性脑损伤大鼠的神经功能缺损。

新生儿缺氧缺血性脑病(HIE)是新生儿死亡或长期神经发育障碍的主要原因,已成为目前临床面临的重大现实问题。然而,其病理生理学和潜在的分子机制尚不清楚。MicroRNA 参与神经元细胞的正常生长和发育。在此,本研究的目的是检查 miR-410-3p 在缺氧缺血后神经功能缺损、神经元损伤和神经元凋亡中的作用,并探讨其相关机制。我们建立了缺氧缺血性脑损伤(HIBD)模型和氧糖剥夺(OGD)模型。Zea-longa评分和TTC染色用于检测HIBD后的急性脑功能障碍。QPCR 验证显示 HIBD 后 24 小时大鼠以及 OGD 后 PC12、SY5Y 细胞和原代皮质神经元的 miR-410-3p 表达显着下调。为了进一步确定 miR-410-3p 的功能,应用慢病毒介导的过表达病毒体内体外. 进行行为测试,包括莫里斯水迷宫、旷场测试、Y 迷宫测试、神经严重程度评分和旋转杆测试,以评估 HIBD 后 1 个月大鼠的长期行为变化。结果表明,OGD 后细胞数量和轴突长度均减少。而在上调miR-410-3p后测量细胞数量和轴突长度的增加。同时,miR-410-3p 过表达抑制神经元凋亡并增强神经元存活。此外,miR-410-3p过表达的HIBD大鼠的长期运动和认知功能显着恢复。总之,miR-410-3p 在保护神经元生长以及促进 HIBD 新生大鼠的运动和认知功能恢复方面发挥着关键作用。

更新日期:2020-07-03
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