Methylmercury alters glutamate transport in astrocytes

Michael Aschner, Chang Ping Yao, Jeffrey W. Allen, Kim H. Tan

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalNeurochemistry International
Volume37
Issue number2-3
DOIs
StatePublished - Aug 1 2000
Externally publishedYes

Fingerprint

Astrocytes
Glutamic Acid
Fishes
Conservation of Natural Resources
Child Development
Mercury
Sweden
Teratology
Psychological Tests
Excitatory Amino Acids
Metallothionein
Quebec
Health Policy
Neurologic Manifestations
Epidemiology
Homeostasis
Eating
Mothers
Interviews
Diet

Keywords

  • Astrocyte
  • Glutamate
  • Metallothionein
  • Methylmercury

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Methylmercury alters glutamate transport in astrocytes. / Aschner, Michael; Yao, Chang Ping; Allen, Jeffrey W.; Tan, Kim H.

In: Neurochemistry International, Vol. 37, No. 2-3, 01.08.2000, p. 199-206.

Research output: Contribution to journalArticle

Aschner, Michael ; Yao, Chang Ping ; Allen, Jeffrey W. ; Tan, Kim H. / Methylmercury alters glutamate transport in astrocytes. In: Neurochemistry International. 2000 ; Vol. 37, No. 2-3. pp. 199-206.
@article{5617e17da6b144f0a088579edda006d7,
title = "Methylmercury alters glutamate transport in astrocytes",
abstract = "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.",
keywords = "Astrocyte, Glutamate, Metallothionein, Methylmercury",
author = "Michael Aschner and Yao, {Chang Ping} and Allen, {Jeffrey W.} and Tan, {Kim H.}",
year = "2000",
month = "8",
day = "1",
doi = "10.1016/S0197-0186(00)00023-1",
language = "English (US)",
volume = "37",
pages = "199--206",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",
number = "2-3",

}

TY - JOUR

T1 - Methylmercury alters glutamate transport in astrocytes

AU - Aschner, Michael

AU - Yao, Chang Ping

AU - Allen, Jeffrey W.

AU - Tan, Kim H.

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

UR - http://www.scopus.com/inward/record.url?scp=0034256934&partnerID=8YFLogxK

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

VL - 37

SP - 199

EP - 206

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 2-3

ER -