miR-214-3p Targets β-Catenin to Regulate Depressive-like Behaviors Induced by Chronic Social Defeat Stress in Mice
miR-214-3p Targets β-Catenin to Regulate Depressive-like Behaviors Induced by Chronic Social Defeat Stress in Mice
复制标题
miR-214-3p 靶向 β-连环蛋白来调节小鼠由慢性社交失败压力引起的抑郁样行为。
DOI：
10.1093/cercor/bhy047
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发表时间：
2019-04-01
期刊：
影响因子：
3.7
通讯作者：
Wang, Fang
中科院分区：
文献类型：
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作者：
Deng, Zhi-Fang;Zheng, Hui-Ling;Wang, Fang
β-连环蛋白与重度抑郁症（MDD）有关，其与突触可塑性和树突树枝化有关。MicroRNA（miRNA）是一类约22个核苷酸的非编码小RNA，参与多种生理和病理生理过程，但其在MDD中的作用尚不清楚。在此，我们研究了miRNAs在慢性社会失败应激（CSDS）小鼠模型中的表达和功能。通过计算机预测、靶基因荧光素酶报告基因分析和神经元转染实验验证了所选miRNA对β-catenin的调控作用。我们证明，CSDS小鼠内侧前额叶皮质（mPFC）中靶向β-连环蛋白转录物的miR-214- 3 p水平显著增加。Antagomir-214- 3 p是一种miR-214- 3 p的中和抑制剂，可增加β-连环蛋白的水平，并逆转CSDS小鼠的抑郁样行为。同时，CSDS小鼠mPFC中微小兴奋性突触后电流（mEPSC）的幅度和树突棘的数量增加，这可能与cldn 1的表达增加有关。此外，鼻内给予antagomir-214- 3 p还显着增加了β-连环蛋白的水平，并逆转了CSDS小鼠的抑郁样行为。这些结果可能代表MDD的新治疗靶点。
beta-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of beta-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons. We demonstrated that the levels of miR-214-3p, which targets beta-catenin transcripts were significantly increased in the medial prefrontal cortex (mPFC) of CSDS mice. Antagomir-214-3p, a neutralizing inhibitor of miR-214-3p, increased the levels of beta-catenin and reversed the depressive-like behavior in CSDS mice. Meanwhile, antagomir-214-3p increased the amplitude of miniature excitatory postsynaptic current (mEPSC) and the number of dendritic spines in mPFC of CSDS mice, which may be related to the elevated expression of cldn1. Furthermore, intranasal administered antagomir-214-3p also significantly increased the level of beta-catenin and reversed the depressive-like behaviors in CSDS mice. These results may represent a new therapeutic target for MDD.