先进的父亲年龄通过m6A修饰介导的代际遗传加剧后代的神经炎症
Yiting Mao1,2,3, Yicong Meng2,4, Kexin Zou2,5
1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
Journal of neuroinflammation
|October 4, 2024
概括
在小鼠中,先进的父亲年龄 (APA) 会导致后代认知障碍和自闭症类行为. 精子中的表观遗传变化,特别是涉及 Nr4a2 的 m6A 修饰和升高的 Ythdc1,有助于神经炎症和行为缺陷.
科学领域:
- 生殖生物学 生殖生物学
- 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.
背景情况:
- 先进的父亲年龄 (APA) 是一个全球趋势,与不良妊娠结果和后代健康问题有关.
- 父亲衰老影响后代神经精神疾病的机制在很大程度上是未知的.
- 这项研究调查了老化精子后代的行为和表观遗传变化.
研究的目的:
- 为了探索先进的父亲年龄 (APA) 老鼠后代的行为表型.
- 为了确定从老化精子中继承的APA后代的病态表观遗传变化.
- 阐明N6-甲基氨酸 (m6A) 修改在代际神经发育影响中的作用.
主要方法:
- 在后代小鼠身上进行了行为测试,ELISA,免疫光和西部涂抹.
- 甲基化RNA免疫沉降测序 (MeRIP-seq) 和RNA免疫沉降测序 (RIP-seq) 分析了精子和海马体中的m6A配置文件.
- 用病毒载体操纵基因表达,以评估神经炎症的治疗点.
主要成果:
- APA后代表现出认知障碍和类似自闭症的行为,增加神经炎症和微质过度活化.
- Nr4a2高甲基化,APA后代的表达减少,影响突触可塑性和微质功能.
- 在老化精子和后代中的Ythdc1升高,海马体识别并抑制了Nr4a2,导致异常表型;Ythdc1抑制缓解了这些缺陷.
结论:
- 先进的父亲年龄与后代的特定行为异常有关.
- 表观遗传修饰,特别是m6A甲基化和像Ythdc1这样的读者蛋白,在神经发育风险的代际传播中发挥作用.
- 向Ythdc1为缓解APA相关后代神经炎症和行为问题提供了潜在的治疗策略.
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