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miR-153下调通过上调遭受单次长时间应激大鼠海马中的西格玛-1受体来减轻创伤后应激障碍样行为并减少细胞凋亡。

MiR-153 downregulation alleviates PTSD-like behaviors and reduces cell apoptosis by upregulating the Sigma-1 receptor in the hippocampus of rats exposed to single-prolonged stress.

作者信息

Chen Yu-Lu, Tong Lei, Chen Yao, Fu Chang-Hai, Peng Jun-Bo, Ji Li-Li

机构信息

Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.

Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.

出版信息

Exp Neurol. 2022 Jun;352:114034. doi: 10.1016/j.expneurol.2022.114034. Epub 2022 Mar 5.

Abstract

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may lead to a series of changes in the central nervous system, including impaired synaptic plasticity, neuronal dendritic spine loss, enhanced apoptosis and increased inflammation. However, the specific mechanism of PTSD has not been studied clearly. In the present study, we found that the level of miR-153-3p in the hippocampus of rats exposed tosingle-prolonged stresss (SPS) was upregulated, but its downstream target σ-1R showed a significant decrease. The downregulation of miR-153 could alleviate the PTSD-like behaviors in the rats exposed to SPS, and this effect might be related to the upregulation of σ-1R and PSD95. Furthermore, anti-miR-153 could also increase the dendritic spine density and reduce cell apoptosis in the hippocampus of SPS rats. In addition, we showed that the mTOR signaling pathway might be involved in the regulation of σ-1R in the hippocampus of rats exposed to SPS. The results of this study indicated that miR-153 might alleviate PTSD-like behaviors by regulating cell morphology and reducing cell apoptosis in the hippocampus of rats exposed to SPS by targeting σ-1R, which might be related to the mTOR signaling pathway.

摘要

创伤后应激障碍(PTSD)是一种精神障碍,可能导致中枢神经系统发生一系列变化,包括突触可塑性受损、神经元树突棘丢失、细胞凋亡增加和炎症反应增强。然而,PTSD的具体机制尚未得到明确研究。在本研究中,我们发现暴露于单次长时间应激(SPS)的大鼠海马中miR-153-3p水平上调,但其下游靶点σ-1R显著降低。下调miR-153可减轻暴露于SPS的大鼠的PTSD样行为,这种效应可能与σ-1R和PSD95的上调有关。此外,抗miR-153还可增加SPS大鼠海马中的树突棘密度并减少细胞凋亡。此外,我们表明mTOR信号通路可能参与了暴露于SPS的大鼠海马中σ-1R的调节。本研究结果表明,miR-153可能通过靶向σ-1R调节暴露于SPS的大鼠海马中的细胞形态并减少细胞凋亡来减轻PTSD样行为,这可能与mTOR信号通路有关。

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