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失调的miR-124调节了由父亲早期社会隔离引起的社会记忆行为受损
Sijia Chen1,2, Shixin Ding1,2, Yingting Pang1,3
1Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, China.
Translational psychiatry
|September 28, 2024
概括
父亲的早期社会隔离 (SI) 通过改变大脑发育,损害后代的社会行为和记忆. 在年轻小鼠中,miR-124的表观遗传传染会影响髓的形成和社会相互作用.
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.
- 发育生物学 发展生物学
背景情况:
- 众所周知,早期的社会孤立 (SI) 会导致成年人的行为异常.
- 父亲SI对后代神经发育和社会行为的代际影响仍然在很大程度上未被探索.
研究的目的:
- 研究父亲早期SI对F1后代的社会行为和神经发育的影响.
- 阐明潜在的分子机制,专注于表观遗传修饰和大脑变化.
主要方法:
- 用小鼠模型研究了父亲早期SI对F1后代的影响.
- 分析包括行为测试 (社会记忆,焦虑),以及中部前额叶皮质 (mPFC) 的分子分析,包括髓,突触和基因/微RNA表达 (miR-124, Nr4a1).
- 研究了通过精子进行表观遗传传染.
主要成果:
- 父亲早期的SI诱导了F1后代的社会记忆缺陷和类似焦虑的行为.
- 在受影响后代的mPFC中观察到髓和突触的变化.
- 在mPFC中对miR-124的下调或其目标 Nr4a1的过度表达改善了社会相互作用和寡细胞成熟.
- 来自SI父亲的精子中升高的miR-124是通过表观遗传传的,影响后代mPFC寡干细胞中的miR-124/Nr4a1/葡萄皮质受体通路,损害了依赖于髓生成的社会行为.
结论:
- 父亲早期的SI通过miR-124介导途径在表观遗传上影响后代的神经发育和社会行为.
- 这项研究揭示了压力效应的代际传播的新机制,影响社会行为和髓形成.
- 针对miR-124/Nr4a1通路为早期生活压力引起的社会行为缺陷提供了潜在的治疗途径.
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