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托皮拉玛酸对神经发育有毒性的机制
John W Steele1,2, Vaishnav Krishnan3, Richard H Finnell1,2,4
1Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, USA.
Critical reviews in toxicology
|July 12, 2024
概括
怀孕期间的托皮拉暴露与儿童患自闭症,智力障碍和多动症的风险增加有关. 需要进一步的研究来了解这些神经发育风险并预防不良结果.
科学领域:
- 神经科学是一个神经科学.
- 发育毒理学 发展毒理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 抗发作药物 (ASM) 的处方正在增加,因为说明范围扩大.
- 人们担心,在暴露于ASM的怀孕中,可能会产生不良的神经发育结果.
- 人口研究表明,托皮拉使用与自闭症谱系障碍 (ASD),智力障碍和注意力缺陷/多动症障碍 (ADHD) 的风险增加有关.
研究的目的:
- 批判性地审查有关托皮拉玛酸的神经行为性致性的流行病学证据.
- 探索托皮拉对神经认知发育影响的潜在神经分子机制.
- 为减少与托皮拉和其他ASM相关的不良妊娠结果的策略提供信息.
主要方法:
- 对大规模人口研究和流行病学证据的审查.
- 对托皮拉与离子通道 (例如GABAergic信号传递) 的药理相互作用的分析.
- 研究托皮拉对表观遗传机制 (DNA甲基化,基因素乙化),氧化应激和胎儿生长的影响.
主要成果:
- 流行病学数据表明,托皮拉暴露与子女患ASD,智力障碍和ADHD风险增加之间存在相关性.
- 潜在的机制包括GABAergic信号的破坏,表观遗传变化,氧化应激和胎儿生长限制.
- 这些因素可能会导致观察到的神经发育毒性.
结论:
- 托皮拉酸盐表现出神经行为病原性,对暴露后代的神经发育构成风险.
- 了解特定的分子通路对于减轻这些风险至关重要.
- 这种知识对于改善使用托皮拉或类似的ASM的妇女的妊娠结果至关重要.
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