产前暴露于1-尼托皮林会导致自闭症类行为,部分原因是通过改变发育中的大脑中的DNA基甲基化
Ting Zhao1,2, Cheng-Qing Huang3, Yi-Hao Zhang1,2
1Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230022, China.
概括
产前暴露于机动车尾气成分1-尼特罗皮烯 (1-NP) 诱导了小鼠通过破坏内部神经元迁移和改变DNA基甲基化来诱导自闭症类行为. 孕产妇服用α-谷氨酸 (α-KG) 补充剂可以减轻这些影响.
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
- 环境健康 环境健康
背景情况:
- 自闭症谱系障碍 (ASD) 是一种神经发育状况,其特征是社会沟通缺陷和重复性行为.
- 机动车尾气含有诸如1-基烯 (1-NP) 这样的污染物,它是神经发育障碍的潜在环境风险因素.
研究的目的:
- 在小鼠模型中检查产前暴露于1-尼托烯 (1-NP) 对自闭症类行为发展的影响.
- 阐明涉及内部神经元迁移和DNA基甲基化的潜在分子机制.
主要方法:
- 使用了一种在产前暴露于1-NP. 的小鼠模型.
- 进行行为测试 (三室测试),电生理学 (补丁),免疫光,以及对基因表达和DNA修饰 (TET活性) 的分子分析.
- 研究了阿尔法谷氨酸 (α-KG) 补充剂的治疗潜力.
主要成果:
- 产前暴露于1-NP导致了类似自闭症的行为,抑制性突触传输减少,并减少了谷氨酸脱酶67 (GAD67) 阳性内部神经元的数量.
- 暴露在1-NP下,通过降低相关基因和抑制十-十一转位 (TET) 活性,降低DNA基甲基化,损害了内部神经元迁移.
- 母亲的α-KG补充剂逆转了1-NP诱导的表观遗传变化,内部神经元迁移缺陷,以及后代的自闭症类行为.
结论:
- 产前暴露于1-尼特罗皮烯是一种潜在的环境风险因素,有助于自闭症类行为.
- 该机制涉及由于关键基因的DNA基甲基化改变而导致的内部神经元迁移受损,由TET酶抑制介导.
- 母亲的α-KG补充剂在预防或改善1-NP诱导的神经发育缺陷和类似自闭症的行为方面表现有前途.
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