Analysis of miRNA expression profiles in amygdala of mice induced by chronic stress in narrow space confinement

Xinwei LUO; Chen BIAN; Wanjun YANG; Maohu ZHOU; Guoyu YANG

doi:10.16016/j.2097-0927.202211005

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Analysis of miRNA expression profiles in amygdala of mice induced by chronic stress in narrow space confinement

Neuroscience | 更新时间：2026-01-09

- Analysis of miRNA expression profiles in amygdala of mice induced by chronic stress in narrow space confinement
- Journal of Army Medical University Vol. 45, Issue 10, Pages: 1060-1069(2023)
- 作者机构：
  
  1.400038重庆，陆军军医大学(第三军医大学)：医学心理系军人发展心理学教研室
  2.400038重庆，陆军军医大学(第三军医大学)：基础医学院神经生物教研室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202211005
  CLC： R338.26;R394.3;R749.72
- Received：01 November 2022，
  
  Revised：2022-12-05，
  
  Published：30 May 2023
- 稿件说明：
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Xinwei LUO, Chen BIAN, Wanjun YANG, et al. Analysis of miRNA expression profiles in amygdala of mice induced by chronic stress in narrow space confinement[J]. Journal of Army Medical University, 2023, 45(10): 1060-1069.
DOI：

Xinwei LUO, Chen BIAN, Wanjun YANG, et al. Analysis of miRNA expression profiles in amygdala of mice induced by chronic stress in narrow space confinement[J]. Journal of Army Medical University, 2023, 45(10): 1060-1069. DOI： 10.16016/j.2097-0927.202211005.

摘要

目的

分析慢性应激诱导的焦虑障碍模型小鼠杏仁核miRNA表达情况，探索在焦虑障碍中发挥作用的关键miRNA及其可能的作用靶点。

方法

选取24只8周龄C57BL/6雄性小鼠(体质量为18~22 g)，采用区组随机法按照体质量分为焦虑障碍组(

=12)和对照组(

=12)。焦虑障碍组采用连续10 d的狭小空间约束方法(每天2 h)用于制造焦虑障碍小鼠模型，对照组无应激。造模完成后采用高架十字迷宫实验、旷场实验、明暗箱实验检测小鼠的焦虑样行为。采用转录组测序方法检测并分析焦虑障碍组小鼠和对照组小鼠杏仁核miRNAs表达情况，结合miRanda对差异表达miRNA靶基因进行预测，并进行功能注释(Gene Ontology，GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)数据库的信号通路分析，探索杏仁核中在焦虑障碍发挥作用的重要miRNA，并对其中关键miRNA进行RT-qPCR检测。

结果

焦虑障碍组小鼠在高架十字迷宫、旷场、明暗箱实验中均表现出显著的焦虑样行为。与对照组比较，焦虑障碍组小鼠杏仁核中共有35条差异表达miRNA。GO功能分析结果显示，预测靶基因在神经元突触可塑性相关功能显著富集。KEGG信号通路分析结果显示，差异miRNA预测靶基因在信号传导

、癌症相关信号通路富集显著。经RT-qPCR检测，miR-128-2-5p在焦虑障碍组的表达显著降低(

0.05)，miR-10b-5p、miR-200a-3p、miR-200b-3p、miR-429-3p在焦虑障碍组的表达显著升高(

0.05)。其中，miR-128-2-5p和miR-200a-3p的改变幅度与转录组测序结果基本一致。

结论

基于生物信息学分析获得的关键miRNA分子miR-128-2-5p及其下游靶基因

bmpr

2、

6、

rbfox

3可能是焦虑障碍潜在的干预治疗靶点。

Abstract

Objective

To analyze the miRNAs expression profile of the amygdala of mice with chronic stress-induced anxiety disorder and explore the key miRNAs and their possible targets.

Methods

Eight-week -old C57BL/6 male mice with body weight ranging from 18 g to 22 g were randomly divided into anxiety disorder group (

=12) and control group (

=12). The anxiety disorder group have been restrained in narrow space for 10 consecutive days (2 h/d) to create a mouse model of anxiety disorder

while the control group accepted no stress. After the modeling was completed

the anxiety-like behavior of mice was detected by elevated cross maze experiment

open field experiment and light and dark box experiment. Transcriptome sequencing was used to detect the expression of miRNAs in the amygdala of mice between the anxiety disorder group and the control group. The target genes of differentially expressed miRNA were predicted by miRanda. Functional annotation was conducted by Gene Ontology (GO) analysis

and signal pathway analysis by Kyoto Encyclopedia of Genes and Genomes (KEGG) database to explore the important miRNAs in the amygdala that play a role in anxiety disorders. The key miRNAs explored before were quantitatively detected by RT-qPCR.

Results

The anxiety disorder group showed significant anxiety-like behavior in elevated cross maze

open field and light and dark box experiments. Compared with the control group

the mice in the anxiety disorder group h

ad 35 differentially expressed miRNAs in the amygdala. The results of GO function analysis showed that the predicted target genes were significantly enriched in the functions related to plasticity regulation of synaptic

while the results of KEGG signal pathway analysis showed that the differential miRNA predicted target genes were obviously enriched in signal transduction and cancer-related signaling pathways. The expression of miR-128-2-5p in the anxiety disorder group was significantly decreased (

0.05)

while the expression of miR-10b-5p

miR-200a-3p

miR-200b-3p and miR-429-3p in the anxiety disorder group were significantly increased (

0.05). Among them

the extents of changes of miR-128-2-5p and miR-200a-3p were consistent with the transcriptome sequencing results.

Conclusion

The key miRNA molecule miR-128-2-5p and its downstream target genes bmpr2

irf6 and

rbfox

3 may become the potential therapeutic targets for anxiety disorders.

关键词

Keywords

references

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