Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

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.

Automated summary

Neurodevelopment is highly sensitive to toxic insults, and there is a lack of evaluation on the potential developmental neurotoxicity (DNT) of most commonly used chemicals. Using human cell-based in vitro systems for testing DNT chemicals can aid in prioritizing them based on their effects on neurodevelopment, but there is a limited number of in vitro models for myelination, which is a fundamental process in neurodevelopment.