Neurotoxic and molecular effects of methylmercury in humans

Abstract

Mercurials are global environmental pollutants deriving from natural processes and anthropogenic activities. Most human exposure to mercury occurs through the intake of fish, shellfish, and sea mammals contaminated with methylmercury. Methylmercury is bioaccumulated and biomagnified in the aquatic food chain and reaches its highest levels in top predatory fish. The neurotoxic hazard posed by methylmercury to humans and the unique susceptibility of the developing brain have been well documented following the mass poisonings occurring in Japan and Iraq. Adult cases of methylmercury poisoning are characterized by the delayed onset of symptoms and by the focal degeneration of neurons in selected brain regions (for example, cerebral cortex and cerebellum). Why the fetus displays different neuropathological effects and a higher sensitivity to methylmercury relative to the adult is still unknown. Depending on the degree of in utero exposure, methylmercury may result in effects ranging from fetal death to subtle neurodevelopmental delays. On the basis of epidemiological studies performed in populations having moderate chronic methylmercury exposure, no definitive consensus has been reached to date on the safety level of maternal exposure during pregnancy. Among the multiple mechanisms believed to contribute to methylmercury neurotoxicity, methylmercury-induced microtubule alterations, oxidative damage, impairment of calcium homeostasis, and the potentiation of glutamatergic neurotransmission are presented in this review.