Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Center for Alternatives to Animal Testing (CAAT-Europe), University of Konstanz, 78464 Konstanz, Germany.
Int J Mol Sci. 2021 Jul 25;22(15):7929. doi: 10.3390/ijms22157929.
Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential. Myelination is a fundamental process in neurodevelopment that should be included in a DNT testing strategy, but there are very few in vitro models of myelination. Thus, there is a need to establish an in vitro myelination assay for DNT. Here, we summarize the routes of myelin toxicity and the known models to study this particular endpoint.
神经发育对有毒物质的侵害非常敏感,人们担心环境化学物质正在导致广泛的亚临床发育性神经毒性 (DNT)。由于大多数常用化学物质缺乏此类信息,因此需要增加 DNT 评估,但监管指南中建议的体内研究对于大规模筛选潜在的 DNT 化学物质并不实用。人们普遍认识到,发育性神经毒性是神经发育过程中基本过程中断的结果,并且使用模拟这些过程的基于人细胞的体外系统的测试策略可以帮助确定具有 DNT 潜力的化学物质的优先级。髓鞘形成是神经发育中的一个基本过程,应该包含在 DNT 测试策略中,但髓鞘形成的体外模型非常少。因此,需要建立用于 DNT 的体外髓鞘形成测定法。在这里,我们总结了髓鞘毒性的途径和已知的研究该特定终点的模型。