Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Int J Mol Sci. 2023 Feb 22;24(5):4338. doi: 10.3390/ijms24054338.
Exposure to chemicals may pose a greater risk to vulnerable groups, including pregnant women, fetuses, and children, that may lead to diseases linked to the toxicants' target organs. Among chemical contaminants, methylmercury (MeHg), present in aquatic food, is one of the most harmful to the developing nervous system depending on time and level of exposure. Moreover, certain man-made PFAS, such as PFOS and PFOA, used in commercial and industrial products including liquid repellants for paper, packaging, textile, leather, and carpets, are developmental neurotoxicants. There is vast knowledge about the detrimental neurotoxic effects induced by high levels of exposure to these chemicals. Less is known about the consequences that low-level exposures may have on neurodevelopment, although an increasing number of studies link neurotoxic chemical exposures to neurodevelopmental disorders. Still, the mechanisms of toxicity are not identified. Here we review in vitro mechanistic studies using neural stem cells (NSCs) from rodents and humans to dissect the cellular and molecular processes changed by exposure to environmentally relevant levels of MeHg or PFOS/PFOA. All studies show that even low concentrations dysregulate critical neurodevelopmental steps supporting the idea that neurotoxic chemicals may play a role in the onset of neurodevelopmental disorders.
暴露于化学物质可能对包括孕妇、胎儿和儿童在内的弱势群体构成更大的风险,这些人可能会患上与有毒物质靶器官相关的疾病。在化学污染物中,甲基汞(MeHg)存在于水生食品中,根据暴露时间和水平,对发育中的神经系统的危害最大。此外,某些人为制造的全氟烷基物质(PFAS),如用于商业和工业产品的全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA),包括纸张、包装、纺织品、皮革和地毯的液体拒水剂,都是发育神经毒物。人们对这些化学物质高水平暴露所引起的有害神经毒性作用有了广泛的了解。但对于低水平暴露可能对神经发育产生的后果知之甚少,尽管越来越多的研究将神经毒性化学物质暴露与神经发育障碍联系起来。然而,毒性的机制尚未确定。在这里,我们综述了使用来自啮齿动物和人类的神经干细胞(NSCs)的体外机制研究,以剖析暴露于环境相关水平的 MeHg 或 PFOS/PFOA 所改变的细胞和分子过程。所有研究都表明,即使是低浓度也会使关键的神经发育步骤失调,这支持了神经毒性化学物质可能在神经发育障碍发病中起作用的观点。