Hippocampal miR-211-5p regulates neurogenesis and depression-like behaviors in the rat
Hippocampal miR-211-5p regulates neurogenesis and depression-like behaviors in the rat
复制标题
海马miR-211- 5 p调控大鼠神经发生和抑郁样行为
DOI：
10.1016/j.neuropharm.2021.108618
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发表时间：
2021-06-07
影响因子：
4.7
通讯作者：
Yu, Shu Yan
中科院分区：
文献类型：
--
作者：
Li, Ye;Fan, Cuiqin;Yu, Shu Yan
新出现的证据表明，microRNAs （miRNAs）参与抑郁症的发病机制，抑郁症是一种由遗传和环境因素相互作用引起的潜在威胁生命和致残的精神障碍。然而，参与抑郁症发病和发展的特定mirna及其潜在的分子机制在很大程度上仍然未知。在本研究中，我们筛选了miRNA表达谱，发现在慢性不可预测轻度应激（CUMS）诱导的抑郁症大鼠模型中，miR-211-5p在齿状回（DG）海马内显著下调。在这些CUMS大鼠中，miR211-5p的缺失伴随着神经发生的减少和细胞凋亡的增加。相比之下，在CUMS大鼠的DG区域上调miR-211-5p可促进神经元神经发生，通过抑制Dyrk1A/STAT3信号通路减少神经元凋亡，并缓解这些CUMS大鼠的抑郁样行为。在DG中敲低miR-211-5p的大鼠中，神经元凋亡增加，神经元再生减少，这些影响伴随着抑郁样行为的诱导。综上所述，我们的研究结果表明，海马DG区miR211-5p水平的改变对大鼠的神经发生、细胞凋亡以及抑郁样行为有显著影响。这些发现提示miR-211-5p/Dyrk1A通路在抑郁症的发病机制中发挥重要作用，可能作为治疗抑郁症的潜在治疗靶点。
Emerging evidence has shown that microRNAs (miRNAs) contribute to the pathogenesis of depression, a potentially life-threatening and disabling mental disorder caused by the interaction of genetic and environmental factors. However, the specific miRNAs and their underlying molecular mechanisms as involved in the pathogenesis and development of depression remain largely unknown. In the present study, we screened miRNA expression profiles and found that miR-211-5p was significantly down-regulated within the dentate gyrus (DG) hippocampus in the chronic unpredictable mild stress (CUMS) induced rat model of depression. Deficits in miR211-5p were accompanied with reductions in neurogenesis and increased apoptosis in these CUMS rats. In contrast, an up-regulation of miR-211-5p within the DG area in CUMS rats promoted neuronal neurogenesis, reduced neuronal apoptosis via suppression of the Dyrk1A/STAT3 signaling pathway and relieved depressionlike behaviors in these CUMS rats. In rats subjected to a knock-down of miR-211-5p in the DG there was an increase in neuronal apoptosis and a decrease in neuronal regeneration, effects which were accompanied with an induction of depression-like behaviors. Taken together, the results of our study reveal that altered levels of miR211-5p in the hippocampal DG area exert a significant impact on neurogenesis, apoptosis and thus depressionlike behaviors in rats. These findings suggest that the miR-211-5p/Dyrk1A pathway plays an important role in the pathogenesis of depression and may serve as a potential therapeutic target for the treatment of depression.