Mechanisms of oxidative stress in methylmercury-induced neurodevelopmental toxicity

Abstract

Methylmercury (MeHg) is a long-lasting organic environmental pollutant that poses a great threat to human health. Ingestion of seafood containing MeHg is the most important way by which it comes into contact with human body, where the central nervous system (CNS) is the primary target of MeHg toxicity. During periods of pre-plus postnatal, in particular, the brain of offspring is vulnerable to specific developmental insults that result in abnormal neurobehavioral development, even without symptoms in mothers. While many studies on neurotoxic effects of MeHg on the developing brain have been conducted, the mechanisms of oxidative stress in MeHg-induced neurodevelopmental toxicity is less clear. Hitherto, no single process can explain the many effects observed in MeHg-induced neurodevelopmental toxicity. This review summarizes the possible mechanisms of oxidative stress in MeHg-induced neurodevelopmental toxicity, highlighting modulation of Nrf2/Keap1/Notch1, PI3K/AKT, and PKC/MAPK molecular pathways as well as some preventive drugs, and thus contributes to the discovery of endogenous and exogenous molecules that can counteract MeHg-induced neurodevelopmental toxicity.

Keywords: Methylmercury; Neural stem cell; Neurodevelopmental toxicity; Notch1; Nrf2; Oxidative stress.