Neurotoxicity and molecular effects of methylmercury

The neurotoxicity of high levels of methylmercury (MeHg) and the high susce ptibility of the developing brain are well established both in humans and e xperimental animals. Prenatally poisoned children display a range of effect s varying from severe cerebral palsy to subtle developmental delays. Still unknown is the lowest dose that impairs neurodevelopment. The primary sourc e of human exposure is the fish. The data obtained so far from epidemiologi cal studies on fish-eating populations are not consistent. A reference dose of 0.1 mug MeHg/kg per day has been established by the U.S. Environmental Protection Agency based on a study on Iraq! children exposed to MeHg in ute ro. However, these exposures occurred at high level for a limited period of time, and consequently were not typical of lower chronic exposure levels a ssociated with fish consumption. Major obstacles for estimation of a thresh old dose for MeHg include the delayed appearance of the neurodevelopmental effects following prenatal exposure and limited knowledge of cellular and m olecular processes underlying these neurological changes. In this respect, a strategy which aims at identifying sensitive molecular targets of MeHg at environmentally relevant levels may prove particularly useful to risk asse ssment. Here some examples of MeHg molecular effects occurring at low doses /concentrations are presented. (C) 2001 Elsevier Science Inc.