The Threat Posed by Environmental Contaminants on Neurodevelopment: What Can We Learn from Neural Stem Cells?

Int J Mol Sci. 2023 Feb 22;24(5):4338. doi: 10.3390/ijms24054338.

Abstract

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.

Keywords: developmental neurotoxicity; epigenetic modifications; methylmercury; molecular mechanisms; neural stem cells (NSCs); neurogenesis; per- and polyfluorinated substances (PFAS).

Publication types

  • Review

MeSH terms

  • Child
  • Female
  • Hazardous Substances / pharmacology
  • Humans
  • Methylmercury Compounds* / toxicity
  • Neural Stem Cells*
  • Neurotoxicity Syndromes*
  • Pregnancy

Substances

  • Methylmercury Compounds
  • Hazardous Substances

Grants and funding

This work was funded by the Swedish Research Council, grant 10815-20-4, the Swedish Brain Foundation (Hjärnfonden), and Karolinska Institutet research funds. The funding organizations had no influence on data collection, presentation, or interpretation of the results.