Manganese accumulation in striatum of mice exposed to toxic doses is dependent upon a functional dopamine transporter

Keith M. Erikson, Carrie E. John, Sara R. Jones, Michael Aschner

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The objective of this study was to determine the importance of the dopamine transporter (DAT) in manganese transport. Excessive manganese exposure is associated with a neurotoxicological disease known as manganism characterized by a specific accumulation of manganese in dopamine-rich brain regions. It has been hypothesized that the DAT mediates this specific transport, but its role in manganese neurotoxicity has not been directly examined. We examined brain tissues from manganese-exposed dopamine transporter knockout (DAT-KO) and wild-type (WT) mice. There was significantly less (p < 0.05) manganese in the striatum of exposed DAT-KO mice compared to WT. However, the absence of a functioning DAT did not affect manganese accumulation in other brain regions examined. Furthermore, both iron and divalent metal transporter levels (two known modulators of brain manganese) were similar between DAT-KO and WT mice in all brain regions. These studies demonstrate that the DAT is involved in the facilitation of striatal manganese accumulation and that it may play a critical role in mediating manganese neurotoxicity.

Original languageEnglish (US)
Pages (from-to)390-394
Number of pages5
JournalEnvironmental Toxicology and Pharmacology
Volume20
Issue number3
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Poisons
Manganese
Brain
Corpus Striatum
Knockout Mice
Modulators
Dopamine
Iron
Metals
Tissue

Keywords

  • Dopamine transporter
  • Manganese
  • Mice
  • Neurotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology

Cite this

Manganese accumulation in striatum of mice exposed to toxic doses is dependent upon a functional dopamine transporter. / Erikson, Keith M.; John, Carrie E.; Jones, Sara R.; Aschner, Michael.

In: Environmental Toxicology and Pharmacology, Vol. 20, No. 3, 11.2005, p. 390-394.

Research output: Contribution to journalArticle

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