TET1通过调节Bcl2DNA基甲基化水平来减轻产前化物引起的认知障碍
Yongle Cai1, Xingdong Zeng1, Mengyan Wu1
1Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
Molecular medicine (Cambridge, Mass.)
|March 26, 2025
概括
产前化物暴露会损害胎儿的神经发育,导致后代的认知缺陷. 这通过减少TET1 (Tet-eleven转位蛋白1) 活性发生,影响DNA基甲基化和神经元亡.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 毒理学 毒理学 毒理学
背景情况:
- 产前暴露于化物与子女的神经发育问题和认知缺陷有关.
- 化物的神经毒性作用背后的确切分子机制尚不清楚.
研究的目的:
- 调查产前化物暴露对神经刺激性,亡,突触可塑性和认知功能的影响.
- 阐明潜在的分子机制,重点关注TET1 (Tet-eleven转位蛋白1) 和它在DNA基甲基化中的作用.
主要方法:
- 在怀孕期间,小鼠暴露于高化 (100 mg/L).
- 评估认知功能,树突脊柱密度,以及后代TET1和PSD95的表达.
- 对神经元亡和作用潜能频率进行了体外研究.
- 研究了TET1和Bcl2促进区之间的相互作用.
- 使用了Tet1淘汰赛小鼠进行比较.
主要成果:
- 在怀孕期间高化物暴露导致后代的认知缺陷.
- 在雄性后代海马中观察到TET1和PSD95的减少表达,以及树突脊柱密度的减少.
- 在体外,化物增加了神经元亡,并降低了自发动作潜力的频率.
- TET1直接与Bcl2促进体结合,影响其DNA基甲基化和表达.
- 化物被淘汰的Tet1小鼠表现出类似于化物暴露的小鼠的认知缺陷.
结论:
- 降低TET1的调节,改变Bcl2基甲基化和增加神经元亡是化物诱导的男性后代神经发育障碍的关键机制.
- 在减轻产前化物暴露的神经毒性影响方面,TET1发挥着至关重要的作用.
- 这些发现为在关键发育时期受到化物影响的分子通路提供了新的见解.
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