文章摘要
李梦佳,卢 涛,周 芹,佟常青,董佳敏,刘 燕,宋月晗.慢性束缚诱导的广泛性焦虑障碍前额叶皮质中miRNA的表达[J].,2022,(9):1601-1608
慢性束缚诱导的广泛性焦虑障碍前额叶皮质中miRNA的表达
Discussion of the Mechanism of MiRNA about Generalized Anxiety Disorders by CRS-induced in the Prefrontal Cortex
投稿时间:2022-01-23  修订日期:2022-02-19
DOI:10.13241/j.cnki.pmb.2022.09.001
中文关键词: 广泛性焦虑症障碍  前额叶皮质  miRNA
英文关键词: Generalized anxiety disorder  The Prefrontal cortex  Micro RNAs
基金项目:国家自然科学基金面上项目(8187150712)
作者单位E-mail
李梦佳 北京中医药大学生命科学学院 北京 100029 jia1273814164@163.com 
卢 涛 北京中医药大学生命科学学院 北京 100029  
周 芹 北京中医药大学生命科学学院 北京 100029  
佟常青 北京中医药大学生命科学学院 北京 100029  
董佳敏 北京中医药大学生命科学学院 北京 100029  
刘 燕 北京中医药大学生命科学学院 北京 100029  
宋月晗 北京中医药大学生命科学学院 北京 100029  
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中文摘要:
      摘要 目的:研究慢性束缚(Chronic restraint stress,CRS)诱导的广泛性焦虑障碍模型小鼠前额叶皮质miRNA表达谱的变化及其意义。方法:小鼠经过7天的CRS,通过旷场实验与高架十字迷宫实验检测小鼠是否能够表现出紧张和焦虑行为。采用高通量测序的方法,定量分析对照组与模型组小鼠前额叶皮质组织中 miRNAs的表达水平,研究CRS诱导的焦虑有关的分子表达谱。通过RT-PCR对测序结果中差异表达的miRNAs 进行验证。结果:经CRS诱导的广泛性焦虑障碍模型组小鼠,模型组在活动总距离增多(P<0.05)、平均速度(P<0.05)增快、中央停留时间减少(P<0.05)、开放臂进入次数百分比减少(P<0.01)、开放臂停留时间减少(P<0.01),与对照组相比结果均具有统计学意义,表明GAD小鼠造模成功。经高通量测序结果及生信学分析,对照组与模型组相比较,共28个上调miRNAs,34个下调miRNAs,5388个靶基因参与作用变化。上/下调的miR-GO分析结果中,主要共同参与神经系统发育、突触后密度、神经元投射、蛋白丝氨酸/苏氨酸激酶活性等过程;上/下调miR-KEGG结果中,参与共同通路主要包括轴突引导、神经营养因子信号通路、cAMP 信号通路、多巴胺能突触、MAPK信号通路等过程。结论:前额叶皮质中miR-7a-5p、miR-124-3p、miR-141-3p、miR-183-5p等miRNA变化参与广泛性焦虑障碍的发病,可能调控影响神经传导等功能。
英文摘要:
      ABSTRACT Objective: To study the changes and significance of miRNA expression profile in the prefrontal cortex of mice with generalized anxiety disorder induced by chronic restraint stress (CRS). Methods: After 7 days of CRS, the mice were tested by open field experiment and elevated plus maze experiment to detect whether the mice can show nervous and anxious behaviors. High-throughput sequencing was used to quantitatively analyze the expression levels of miRNAs in the prefrontal cortex of mice in the control and model groups, and to study the molecular expression profiles related to anxiety induced by CRS. The differentially expressed miRNAs in the sequencing results were verified by RT-PCR. Results: In mice in the CRS-induced generalized anxiety disorder model group, the total distance of activities in the model group increased (P<0.05), the average speed (P<0.05) increased, the central residence decreased (P<0.05), and the percentage of open arm entry times (P<0.01) and residence time of the open arm (P<0.01)are reduced. Compared with the control group, the results were statistically significant, indicating that the GAD mice were successfully modeled. Based on the results of high-throughput sequencing and bio-informatics analysis, compared with the control group, there were 28 up-regulated miRNAs and 34 down-regulated miRNAs in the model group and 5388 target genes participated in the changes. In the up/down-regulated miR-GO analysis results, they are mainly involved in the development of the nervous system, postsynaptic density, neuron projection, protein serine/threonine kinase activity and other processes; in the up/down-regulated miR-KEGG results, they participate in common pathways Mainly include axon guidance, neurotrophic factor signaling pathway, cAMP signaling pathway, dopaminergic synapse, MAPK signaling pathway and so on. Conclusion: The changes of miR-7a-5p, miR-124-3p, miR-141-3p, miR-183-5p and other miRNAs in the prefrontal cortex are involved in the pathogenesis of generalized anxiety disorder, and may regulate and affect nerve conduction functions.
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