The Effects of Low-Dose Methylmercury Exposure in Regulating Murine Embryonic Neural Precursor Development

Abstract

Methylmercury (MeHg) is a global pollutant that affects millions of people worldwide. It is known to be neurotoxic, particularly during fetal development. Numerous cohort studies have shown correlations between impaired cognitive development and prenatal exposure to methylmercury by fish intake during pregnancy. However, the mechanisms responsible for MeHg-induced changes in adult neuronal function, when their exposure occurred primarily during fetal development, are not yet understood. We hypothesize that fetal MeHg exposure could affect neural precursor development leading to long-term neurotoxic effects. In this project, we exposed mouse primary cortical precursors in vitro to a range of methylmercury doses at nano- and subnano-molar level and examine the effect they have on embryonic neural precursor development. We observed that cortical precursor exposed to 0.25 nM MeHg showed increased neuronal differentiation, while its proliferation was inhibited. Reduced neuronal differentiation, however, was observed in the higher dose groups. RT-qPCR results also revealed that cell reprogramming was taking place for the cortical precursors exposed to 5nM MeHg treatment. Our results suggest that sub-nanomolar MeHg exposure may deplete the pool of neural precursors by increasing premature neuronal differentiation, which can lead to long-term neurological effects in adulthood as opposed to the higher MeHg doses that cause more immediate toxicity during infant development.