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miR-150 在应激诱导的小鼠焦虑样行为中的作用。

The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice.

机构信息

Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Tongzipo Road 172, Changsha, Hunan, China.

Clinical Anatomy & Reproductive Medicine Application Institute, University of South China, Hengyang, China.

出版信息

Neurotox Res. 2019 Jan;35(1):160-172. doi: 10.1007/s12640-018-9943-x. Epub 2018 Aug 17.

DOI:10.1007/s12640-018-9943-x
PMID:30120712
Abstract

Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.

摘要

压力在多种精神疾病中起着关键作用,包括焦虑症。然而,其潜在机制仍知之甚少。在这里,我们使用急性应激(AS)和慢性束缚应激(CRS)模型来诱发类似焦虑的行为,并研究 miR-150 在小鼠海马中的作用。评估了皮质酮水平以及海马中的谷氨酸受体。我们发现,无论是 AS 还是 CRS 后,都会引起类似焦虑的行为,通过旷场试验(OFT)和高架十字迷宫试验(EPM)来确定。AS 和 CRS 组的血液中皮质酮水平升高,而海马中 miR-150 mRNA 的表达显著降低。无论是 AS 还是 CRS,海马中的 GluN2A、GluR1、GluR2 和 V-Glut2 表达均降低。AS 增加了海马中的 GAD67 表达,但 CRS 没有,CRS 降低了 GluN2B 表达,但 AS 没有。成年 miR-150 敲除小鼠表现出类似焦虑的行为,通过 OFT 和 EPM 来评估。海马中的 GluN2A、GluN2B、GluR1 和 GluR2 的表达也下调,但 miR-150 敲除小鼠的 V-Glut2 表达上调。有趣的是,我们发现与野生型小鼠相比,miR-150 敲除小鼠的海马中树突长度、树突分支和树突棘数量减少。这些结果表明,miR-150 可能影响海马的突触可塑性,并在成年小鼠应激诱导的类似焦虑行为中发挥重要作用。

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