Mechanisms of methylmercury-induced neurotoxicity

Evidence from experimental studies

Marcelo Farina, João B T Rocha, Michael Aschner

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle.

Original languageEnglish (US)
Pages (from-to)555-563
Number of pages9
JournalLife Sciences
Volume89
Issue number15-16
DOIs
StatePublished - Oct 10 2011
Externally publishedYes

Fingerprint

Oxidative stress
Toxicity
Brain
Selenoproteins
Nervous System Diseases
Mitochondria
Neurotoxins
Oxidative Stress
Homeostasis
Biochemical Phenomena
Fish
Glutamic Acid
Animals
Cells
Tissue
Calcium
Poisoning
Molecules
Cultured Cells
Rodentia

Keywords

  • Calcium
  • Glutamate
  • Glutathione peroxidase
  • Methylmercury
  • Neurotoxicity
  • Oxidative stress
  • Selenium
  • Selenoproteins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Mechanisms of methylmercury-induced neurotoxicity : Evidence from experimental studies. / Farina, Marcelo; Rocha, João B T; Aschner, Michael.

In: Life Sciences, Vol. 89, No. 15-16, 10.10.2011, p. 555-563.

Research output: Contribution to journalArticle

Farina, Marcelo ; Rocha, João B T ; Aschner, Michael. / Mechanisms of methylmercury-induced neurotoxicity : Evidence from experimental studies. In: Life Sciences. 2011 ; Vol. 89, No. 15-16. pp. 555-563.
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