Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity

Michael Aschner, T. Syversen, D. O. Souza, J. B T Rocha, M. Farina

Research output: Contribution to journalReview article

197 Citations (Scopus)

Abstract

This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage.

Original languageEnglish (US)
Pages (from-to)285-291
Number of pages7
JournalBrazilian Journal of Medical and Biological Research
Volume40
Issue number3
DOIs
StatePublished - 2007
Externally publishedYes

Fingerprint

Astrocytes
Glutamic Acid
Reactive Oxygen Species
Oxidative stress
Oxidative Stress
Mitochondria
Immediate-Early Genes
Synaptosomes
Cytotoxicity
Heat-Shock Proteins
Cell culture
Cerebellum
Rats
Rodentia
Brain
Phosphotransferases
Cell Culture Techniques
Antioxidants
Genes
Chemical activation

Keywords

  • Astrocytes
  • Glutamate and selenocompounds
  • Methylmercury neurotoxicity
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biophysics
  • Neuroscience(all)
  • Biochemistry
  • Physiology
  • Immunology
  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Cell Biology

Cite this

Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. / Aschner, Michael; Syversen, T.; Souza, D. O.; Rocha, J. B T; Farina, M.

In: Brazilian Journal of Medical and Biological Research, Vol. 40, No. 3, 2007, p. 285-291.

Research output: Contribution to journalReview article

Aschner, Michael ; Syversen, T. ; Souza, D. O. ; Rocha, J. B T ; Farina, M. / Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. In: Brazilian Journal of Medical and Biological Research. 2007 ; Vol. 40, No. 3. pp. 285-291.
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