叶酸可以防止与自闭症相关的表型,这是由于草原的发育性甲状腺暴露引起的
Nilanjana Saferin1, Ibrahim Haseeb2, Adam M Taha3
1Department of Neurosciences and Psychiatry, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
bioRxiv : the preprint server for biology
|December 9, 2024
概括
发育性甲状腺农药暴露 (DPE) 通过改变叶酸代谢导致神经发育缺陷. 母亲的叶酸补充剂有效地减少了后代的这些影响,突出了环境风险因素的潜在预防策略.
科学领域:
- 环境毒理学环境毒理学
- 神经科学是一个神经科学.
- 发育生物学是发展生物学.
背景情况:
- 神经发育障碍 (NDD) 影响六分之一的儿童,其原因往往不清楚.
- 发育期暴露于甲状腺农药是NDDs的新兴环境风险因素.
- 以前的研究将低剂量慢性甲状腺暴露与大脑中改变的叶酸代谢物联系起来.
研究的目的:
- 调查发育性甲状腺暴露 (DPE) 是否直接影响叶酸代谢.
- 为了确定高剂量的母体叶酸补充剂是否可以预防或减轻DPE诱导的生物行为影响.
- 研究DPE和叶酸补充剂对特定叶酸通路酶和蛋白质的影响.
主要方法:
- 怀孕的草原被暴露在deltamethrin (一种类杀虫剂) 中,有或没有补充甲基叶酸盐.
- 在五个与NDD相关的领域中评估了后代的行为.
- 分析了血叶酸水平和叶酸相关蛋白质 (SHMT1,FOLR1,MTHFR) 的神经表达.
主要成果:
- DPE后代表现出显著的行为缺陷,血叶酸增加,神经SHMT1表达升高.
- 母亲的叶酸补充剂预防了大多数行为缺陷,除了重复性行为.
- 叶酸补充诱导神经FOLR1和MTHFR表达的补偿性变化.
结论:
- 发育性甲状腺暴露会诱导与NDD相关的行为缺陷,并改变叶酸代谢.
- 孕产妇补充叶酸是一种有效的预防性干预,可以减少但不能完全消除DPE的行为影响.
- 向叶酸代谢提供了一个有希望的策略,以减轻与NDD相关的环境风险.
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