miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1.
miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1.
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miR-34b 通过靶向 CRHR1 减轻创伤引起的焦虑样行为
DOI：
10.3892/ijmm.2017.2981
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发表时间：
2017-07
影响因子：
5.4
通讯作者：
Tian Z
中科院分区：
文献类型：
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作者：
Zhu J;Chen Z;Tian J;Meng Z;Ju M;Wu G;Tian Z
创伤暴露是焦虑的一个潜在诱因；然而，创伤诱发焦虑的分子机制仍需进一步阐明。在本研究中，为了探索这些机制，我们在使用特异性促肾上腺皮质激素释放激素受体1（CRHR1）拮抗剂NBI - 27914干预后的大鼠模型中，通过放射免疫分析法观察下丘脑 - 垂体 - 肾上腺（HPA）轴的变化，并通过旷场试验和高架十字迷宫试验观察焦虑样行为的变化。发现CRHR1参与了创伤诱发的焦虑。然后我们应用生物信息学分析来筛选靶向CRHR1的微小RNA（miRNA或miR），并确定miR - 34b在原代下丘脑神经元中对CRHR1 mRNA起负调控作用。通过药物递送系统使用miRNA模拟物在室旁核（PVN）中过表达miR - 34b，可降低HPA轴的过度活跃以及焦虑样行为。总体而言，本研究证明了HPA轴参与创伤诱发的焦虑，并且通过miR - 34b靶向CRHR1降低HPA轴的过度活跃可减轻创伤诱发的焦虑。
Exposure to trauma is a potential contributor to anxiety; however, the molecular mechanisms responsible for trauma-induced anxiety require further clarification. In this study, in an aim to explore these mechanisms, we observed the changes in the hypothalamic pituitary adrenal (HPA) axis using a radioimmunoassay and the changes in anxiety-like behavior using the open field test and elevated plus maze test in a rat model following intervention with NBI-27914, a specific corticotropin-releasing hormone receptor 1 (CRHR1) antagonist. CRHR1 was found to be involved in trauma-induced anxiety. We then applied bioinformatic analysis to screen microRNAs (miRNAs or miRs) that target CRHR1, and miR-34b was determined to negatively regulate CRHR1 mRNA in primary hypothalamic neurons. The overexpression of miR-34b in the paraventricular nucleus (PVN) by a miRNA agomir using a drug delivery system decreased the hyperactivity of the HPA axis and anxiety-like behavior. Overall, the involvement of the HPA axis in trauma-induced anxiety was demonstrated, and trauma-induced anxiety was attenuated by decreasing the hyperactivity of the HPA axis via miR-34b by targeting CRHR1.