慢性母亲暴露于低剂量的PM2.5会影响认知结果以性别依赖的方式
Brian G Oliver1, Xiaomin Huang2, Rochelle Yarak3
1School of Life Sciences, Faculty of Science, University of Technology Sydney, NSW, Australia; Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
Environment international
|August 24, 2024
概括
产前暴露于交通污染 (PM2.5) 损害男性大脑发育和记忆力. 然而,女性表现出具有保护性的表观遗传变化,特别是涉及素脱甲基酶,这可以防止这些神经系统缺陷.
科学领域:
- 环境健康 环境健康
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
背景情况:
- 空气污染,特别是与交通有关的颗粒物 (PM2.5),对人类健康构成风险,即使在低水平.
- 通过PM2.5影响子宫内发育的机制,特别是神经结果,尚未完全理解.
- 越来越多地认识到对环境毒素反应的性别特异性差异.
研究的目的:
- 研究与交通相关的PM2.5产前暴露对后代大脑发育和认知功能的影响.
- 探索与PM2.5暴露相关的潜在分子机制,包括与性别相关的差异.
- 为了确定潜在的保护因素,防止PM2.5诱导的神经毒性.
主要方法:
- 在交配,怀孕和哺乳期间,BALB/c小鼠暴露在交通PM2.5中.
- 在成年男性和女性后代中评估认知功能 (记忆).
- 脑组织分析包括氧化应激标志物,线粒体功能和RNA测序.
- 使用初级胎儿皮层神经元来测试PM2.5和特定基因的影响.
主要成果:
- 男性后代在成年时表现出记忆功能减弱,而女性则表现出正常的记忆.
- 母亲的PM2.5暴露导致了男性大脑的氧化应激和线粒体异常,而不是女性大脑.
- RNA测序揭示了女性大脑中X染色体链接的基因组脱甲基酶 (Kdm6a,Kdm5c) 和神经保护基因的更高表达.
- 在试验室中,暴露于PM2.5抑制了神经元和突触数量,这种效应通过Kdm6a或Kdm5c上调来阻止.
结论:
- 在出生前通过基因组脱甲基的表观遗传适应可以保护女性免受产前PM2.5诱导的神经损伤.
- 男性缺乏这些保护性表观遗传变化,与受损认知结果相关.
- 这些发现突出了性别特异性的脆弱性和对环境神经毒素的保护机制.
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