生命早期的压力改变了VTA中的染色质修饰,使得压力敏感度成为主要的压力敏感度
bioRxiv : the preprint server for biology
|April 1, 2024
概括
早期的压力会导致大脑多巴胺系统的长期表观遗传变化. 这些分子变化增加了对未来压力的敏感性,增加了情绪和焦虑障碍的风险.
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.
- 分子精神病学分子精神病学
背景情况:
- 生命早期的压力 (ELS) 诱导长期对压力的过敏.
- 驱动这种持续压力敏感性的分子机制仍然不清楚.
- 人们假设表观遗传修饰,特别是染色质变化,可以调解这些效应.
研究的目的:
- 为了研究表观基因组修饰在ELS后腹膜区域 (VTA) 的作用.
- 确定VTA中的表观遗传变化是否将ELS与长期压力过敏性联系起来.
- 为了确定特定的表观遗传标记和酶参与调解ELS诱导的压力敏感性.
主要方法:
- 使用了ELS的小鼠模型.
- 采用质谱学,表观基因组编辑,RNA测序和电生理学.
- 专注于VTA,一个关键的多巴胺作用的大脑区域.
主要成果:
- 在VTA中,ELS改变了基因组的动态,特别是丰富了基因组-3氨-4单甲基化 (H3K4me1) 和酶Setd7.
- 人工模仿ELS诱导的表观遗传变化 (Setd7过度表达,H3K4me1丰富) 在对成人压力敏感的VTA小鼠中.
- 这些表观遗传变化与转录,生理和行为应激反应的变化有关.
结论:
- 在VTA的多巴胺能电路中,ELS会诱导持久的表观遗传变化.
- 这些表观遗传修饰,特别是H3K4me1和Setd7,调解长期压力过敏.
- 这提供了一个分子机制,将ELS与情绪和焦虑障碍的风险增加联系起来.
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