Methylmercury alters glutamate transport in astrocytes

Methylmercury (MeHg) is a significant environmental contaminant that will c ontinue to pose great risk to human health. Considerable attention in the s cientific and health policy fora is focused on the question of whether MeHg intake from a diet high in fish is associated with aberrant CNS function. A number of recent studies (Kjellstrom et al., 1986: Kjellstrom, T., Kenned y, P., Wallis, S., Mantell, C., 1986. Physical and mental development of ch ildren with prenatal exposure to mercury from fish. Stage I: preliminary te sts at age 4. Solna, Sweden. National Swedish Environmental Protection Boar d Report 3080, 1989. Kjellstrom, T., Kennedy, P., Wallis, S., Stewart, A., Friberg, L. et al., 1989. Physical and mental development of children with prenatal exposure to mercury from fish. Stage II: interviews and psychologi cal tests at age 6. Solna, Sweden. National Swedish Environmental Protectio n Board Report 3642; McKeown-Eyssen et al., 1983: McKeown-Eyssen, G., Ruedy , J., Neims, A., 1983. Methylmercury exposure in Northern Quebec II: neurol ogic findings in children. American Journal of Epidemiology 118, 470-479; G randjean ct al., 1997: Grandjean, P., Weihe, P., White, R. F., Debes, F., A raki, S., Yokoyama, K., Murata, K., Sorensen, N., Dahl, R., Jorgensen, P. J ., 1997. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicology and Teratology 19, 417-428) suggest that fe tal exposure at levels attained by mothers eating fish regularly during pre gnancy are associated with neurological deficits in their offspring. Astroc ytes play a key role in MeHg-induced excitotoxicity. (1) MeHg preferentiall y accumulates in astrocytes. (2) MeHg potently and specifically inhibits gl utamate uptake in astrocytes. (3) Neuronal dysfunction is secondary to dist urbances in astrocytes. (4) Go-application of nontoxic concentrations of Me Hg and glutamate leads to the typical appearance of neuronal lesions associ ated with excitotoxic stimulation. (5) MeHg induces swelling of astrocytes. These observations are fully consistent with MeHg-induced dysregulation of excitatory amino acid homeostasis, and indicate that a glutamate-mediated excitotoxic mechanism is involved. This manuscript details the role of astr ocytes in mediating MeHg-induced excitotoxicity, and elaborates on the prot ective role afforded by metallothioneins (MTs) in attenuating MeHg cytotoxi city. (C) 2000 Elsevier Science Ltd. All rights reserved.