在被母亲分离的老鼠中,前额叶皮质的早期逆境诱导的表观遗传重编程
Aleena Francis1, Lauren Allen McKibben2, Yogesh Dwivedi1
1Department of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Biological psychiatry global open science
|May 9, 2025
概括
早期的逆境 (ELA) 导致持久的表观遗传变化. 在老鼠中,母体分离改变了大脑区域的DNA甲基化,影响了与神经发育和压力相关的基因,为精神疾病提供了洞察力.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 早期的逆境 (ELA) 可以通过表观遗传机制诱导持久的行为和神经生物学变化.
- 在动物模型中,母体分离 (MS) 是研究ELA效应的常见范式.
- 前额叶皮质是关键的大脑区域,与应激反应和情绪调节有关.
研究的目的:
- 在MS之后,全面地绘制大鼠前额叶皮质中全基因组DNA甲基化的图谱.
- 为了确定与ELA相关的特定差异甲基化细胞因子 (DMCs) 和区域 (DMRs).
- 探索这些表观遗传变化对基因表达和通路的功能后果.
主要方法:
- 幼鼠经历了母体分离 (180分钟/天,产后1-14天).
- 成年老鼠被评估为抑郁和焦虑类行为.
- 减少代表性双硫酸盐测序用于全基因组DNA甲基化分析,包括非CpG位点.
- 进行了功能分析,包括基因本体学和通路分析.
主要成果:
- 母亲分离导致前额叶皮层发生显著的表观遗传变化,发现了33,905种DMC和151种DMR.
- 参与神经发育,突触可塑性和应激反应途径的基因表现出改变的甲基化.
- 关键受影响的基因包括Dnmt3a/b,Notch1,Mapk14和通道子单元.
- 不同的非CpG甲基化失调了Wnt通路基因,在DMR中丰富了Elk1转录因子结合位.
结论:
- 这项研究提供了一个详细的前额叶皮质的表观遗传地图后,早期的生活逆境.
- 研究结果阐明了导致长期ELA影响的分子机制,并确定了与压力相关疾病的潜在生物标志物.
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