m6A甲基转移酶样蛋白14在抑郁样小鼠海马中的表达

doi:10.16352/j.issn.1001-6325.2024.10.1376

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (10): 1376-1382.doi: 10.16352/j.issn.1001-6325.2024.10.1376

m⁶A甲基转移酶样蛋白14在抑郁样小鼠海马中的表达

杨琳¹, 曲智^1,2, 王源^1,2, 易文学^1,3, 辛锦^1,3, 尹小暖^1,3, 段东晓^1*

郑州大学 1.基础医学院生理学和神经生物学系;
2.医学院医学检验系;
3.医学院临床医学系, 河南郑州 450051

收稿日期:2024-01-18 修回日期:2024-05-29 出版日期:2024-10-05 发布日期:2024-09-27
通讯作者: ^* dongxiaoduan@zzu.edu.cn
基金资助:
河南省科技攻关项目(192102310084,222102310143);郑州大学2022年度大学生创新创业训练计划项目(2022cxcy706)

Expression of m⁶A-modified methyltransferase-like 14 in the hippocampus of depression-like mice

YANG Lin¹, QU Zhi^1,2, WANG Yuan^1,2, YI Wenxue^1,3, XIN Jin^1,3, YIN Xiaonuan^1,3, DUAN Dongxiao^1*

1. Department of Physiology and Neurobiology, Basic Medical School;
2. Department of Medical Laboratory,Medical College;
3. Department of Clinical Medicine,Medical College, Zhengzhou University,Zhengzhou 450051,China

Received:2024-01-18 Revised:2024-05-29 Online:2024-10-05 Published:2024-09-27
Contact: ^* dongxiaoduan@zzu.edu.cn

摘要/Abstract

摘要： 目的研究m⁶A甲基转移酶样蛋白14(METTL14)在抑郁样小鼠海马中的表达变化和作用。方法 1)将C57BL/6J小鼠分为对照组和抑郁模型组。单笼单只饲养并加以不定期慢性不可预知刺激(CUMS),制备抑郁模型时间为4个月。2)用强迫游泳实验(FST)、蔗糖偏好实验(SPT)、悬尾实验 (TST)测试模型小鼠的抑郁样行为。3)行为学检测完成后,取两组小鼠的海马组织,用qRT-PCR、Western blot、Dot blot、免疫组化及免疫荧光等技术检测小鼠海马组织m⁶A修饰及甲基化转移酶样蛋白METTL14的表达。结果 1)模型组小鼠出现明显的抑郁样行为;2)模型组小鼠海马组织中METTL14表达量在mRNA水平升高并伴随m⁶A修饰水平升高;3)模型组小鼠海马CA1、CA3及DG区METTL14蛋白表达量升高且存在神经元损伤现象。结论抑郁样小鼠海马区m⁶A甲基化功能活跃。

关键词: N6-甲基腺苷, 甲基转移酶样蛋白14, 抑郁症, RNA修饰

Abstract: Objective To investigate the expression of m⁶A methyltransferase-like protein 14(METTL14) in the hippocampus of depression-like mice, and to provide a theoretical basis for further study of the molecular mechanism of depression and new drug targets. Methods 1)Twenty-four male C57BL/6J mice were divided into control group and depression model group. The control group was fed normally, and the model group was kept in single animal cage for 4 months and added with Chronic Unpredictable Animal Stress (CUMS) to establish the depression-like model. 2)After modeling, depression-like behaviors in model group were tested using forced swimming test (FST), sucrose preference test (SPT)and tail suspension test (TST).3)Twenty-four hours after completion of behavioral test, the hippocampus tissues of mice were collected, and the expression of m⁶A methyltransferase-like protein METTL14 in the hippocampus of mice was detected by molecular biology experiments. Results 1)The mice in the model group showed significant depression-like behavior; 2)The expression of METTL14 in the hippocampus of the model group showed an increased mRNA expression with the increased m⁶A modification. 3)In the model group, the expression of METTL14 in hippocampal CA1, CA3 and DG districts increased and there was neuronal damage found. Conclusions m⁶A methylation function has been proved to be more active in the hippocampus of depressed mice.

Key words: N6-methyladenosine, methyltransferase-like protein 14(METTL14), depression disorder, RNA modification

中图分类号:

R749.4

杨琳, 曲智, 王源, 易文学, 辛锦, 尹小暖, 段东晓. m⁶A甲基转移酶样蛋白14在抑郁样小鼠海马中的表达[J]. 基础医学与临床, 2024, 44(10): 1376-1382.

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m⁶A甲基转移酶样蛋白14在抑郁样小鼠海马中的表达

Expression of m⁶A-modified methyltransferase-like 14 in the hippocampus of depression-like mice

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