TY - JOUR
T1 - Methylmercury alters glutamate transport in astrocytes
AU - Aschner, Michael
AU - Yao, Chang Ping
AU - Allen, Jeffrey W.
AU - Tan, Kim H.
N1 - Funding Information:
This study was supported in part by PHS grants NIEHS 07331 awarded to MA. JWA was supported by a NIAAA training grant (T32 AA07565). KHT was supported by RIMI NCRR (PO2RR22583).
PY - 2000/8/1
Y1 - 2000/8/1
N2 - Methylmercury (MeHg) is a significant environmental contaminant that will continue to pose great risk to human health. Considerable attention in the scientific 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., Kennedy, P., Wallis, S., Mantell, C., 1986. Physical and mental development of children with prenatal exposure to mercury from fish. Stage I: preliminary tests at age 4. Solna, Sweden. National Swedish Environmental Protection Board 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 psychological tests at age 6. Solna, Sweden. National Swedish Environmental Protection Board Report 3642; McKeown-Eyssen et al., 1983: McKeown-Eyssen, G., Ruedy, J., Neims, A., 1983. Methylmercury exposure in Northern Quebec II: neurologic findings in children. American Journal of Epidemiology 118, 470-479; Grandjean et al., 1997: Grandjean, P., Weihe, P., White, R. F., Debes, F., Araki, 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 fetal exposure at levels attained by mothers eating fish regularly during pregnancy are associated with neurological deficits in their offspring. Astrocytes play a key role in MeHg-induced excitotoxicity. (1) MeHg preferentially accumulates in astrocytes. (2) MeHg potently and specifically inhibits glutamate uptake in astrocytes. (3) Neuronal dysfunction is secondary to disturbances in astrocytes. (4) Co-application of nontoxic concentrations of MeHg and glutamate leads to the typical appearance of neuronal lesions associated 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 astrocytes in mediating MeHg-induced excitotoxicity, and elaborates on the protective role afforded by metallothioneins (MTs) in attenuating MeHg cytotoxicity. (C) 2000 Elsevier Science Ltd.
AB - Methylmercury (MeHg) is a significant environmental contaminant that will continue to pose great risk to human health. Considerable attention in the scientific 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., Kennedy, P., Wallis, S., Mantell, C., 1986. Physical and mental development of children with prenatal exposure to mercury from fish. Stage I: preliminary tests at age 4. Solna, Sweden. National Swedish Environmental Protection Board 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 psychological tests at age 6. Solna, Sweden. National Swedish Environmental Protection Board Report 3642; McKeown-Eyssen et al., 1983: McKeown-Eyssen, G., Ruedy, J., Neims, A., 1983. Methylmercury exposure in Northern Quebec II: neurologic findings in children. American Journal of Epidemiology 118, 470-479; Grandjean et al., 1997: Grandjean, P., Weihe, P., White, R. F., Debes, F., Araki, 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 fetal exposure at levels attained by mothers eating fish regularly during pregnancy are associated with neurological deficits in their offspring. Astrocytes play a key role in MeHg-induced excitotoxicity. (1) MeHg preferentially accumulates in astrocytes. (2) MeHg potently and specifically inhibits glutamate uptake in astrocytes. (3) Neuronal dysfunction is secondary to disturbances in astrocytes. (4) Co-application of nontoxic concentrations of MeHg and glutamate leads to the typical appearance of neuronal lesions associated 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 astrocytes in mediating MeHg-induced excitotoxicity, and elaborates on the protective role afforded by metallothioneins (MTs) in attenuating MeHg cytotoxicity. (C) 2000 Elsevier Science Ltd.
KW - Astrocyte
KW - Glutamate
KW - Metallothionein
KW - Methylmercury
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UR - http://www.scopus.com/inward/citedby.url?scp=0034256934&partnerID=8YFLogxK
U2 - 10.1016/S0197-0186(00)00023-1
DO - 10.1016/S0197-0186(00)00023-1
M3 - Article
C2 - 10812205
AN - SCOPUS:0034256934
SN - 0197-0186
VL - 37
SP - 199
EP - 206
JO - Neurochemistry International
JF - Neurochemistry International
IS - 2-3
ER -