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miRNA-199a-5p 通过靶向 WNT2 调控 CREB/BDNF 信号通路对海马神经元抑郁样发生发挥作用。

MiRNA-199a-5p targets WNT2 to regulate depression through the CREB/BDNF signaling in hippocampal neuron.

机构信息

Department of Graduate School, Tianjin Medical University, Tianjin, China.

Department of department of neurology, The Second Affiliated Hospital of Baotou Medical College, Baotou, China.

出版信息

Brain Behav. 2021 Aug;11(8):e02107. doi: 10.1002/brb3.2107. Epub 2021 Aug 1.

Abstract

INTRODUCTION

This study mainly investigated the role of miR-199a-5p in depression.

METHODS

qRT-PCR and western blotting were employed to detect the expressions of miR-199a-5p, CREB and BDNF. Sucrose preference test, forced swimming test, and tail suspension test were performed to evaluate depression-related symptoms. MTT assays and flow cytometry were used to examine the cell reproduction and apoptotic cells of hippocampal neuron.

RESULTS

The data demonstrated that the expression levels of miR-199a-5p in the cerebrospinal fluids and serums of depression patient and the hippocampus of chronic unpredictable mild stress (CUMS) mouse were significantly increased. However, the expressions of WNT2, p-CREB, and BDNF were inhibited. In addition, miR-199a-5p-inhibitor enhanced sucrose preferences of CUMS mouse and decreased immobile time in sucrose preference test and forced swimming test. Knockdown of WNT2 attenuated the effects of miR-199a-5p-inhibitor on cell reproduction and apoptotic cells of hippocampal neuron and the expression of WNT2, p-CREB, and BDNF.

CONCLUSION

MiR-199a-5p can target WNT2 to enhance the development of depression through regulation of the CREB/BDNF signaling.

TRIAL REGISTRATION

JNU-Hos-49284.

摘要

简介

本研究主要探讨了 miR-199a-5p 在抑郁症中的作用。

方法

采用 qRT-PCR 和 Western blot 检测 miR-199a-5p、CREB 和 BDNF 的表达。通过蔗糖偏好试验、强迫游泳试验和悬尾试验评估抑郁相关症状。MTT 试验和流式细胞术检测海马神经元的细胞增殖和凋亡细胞。

结果

数据表明,抑郁症患者脑脊液和血清中以及慢性不可预测轻度应激(CUMS)小鼠海马中的 miR-199a-5p 表达水平明显升高,而 WNT2、p-CREB 和 BDNF 的表达受到抑制。此外,miR-199a-5p 抑制剂增强了 CUMS 小鼠的蔗糖偏好,并减少了蔗糖偏好试验和强迫游泳试验中的不动时间。WNT2 的敲低减弱了 miR-199a-5p 抑制剂对海马神经元细胞增殖和凋亡细胞以及 WNT2、p-CREB 和 BDNF 表达的影响。

结论

miR-199a-5p 可以通过调节 CREB/BDNF 信号通路靶向 WNT2 来增强抑郁症的发生。

试验注册号

JNU-Hos-49284。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d5c/8413827/20864e6b6b7e/BRB3-11-e02107-g001.jpg

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