Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia

Gregg D. Stanwood, Duncan B. Leitch, Valentina Savchenko, Jane Wu, Vanessa A. Fitsanakis, Douglas J. Anderson, Jeannette N. Stankowski, Michael Aschner, Bethann McLaughlin

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson's disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alterations induced by manganese exposure. Primary mesencephalic cultures were treated with 10-800 μM manganese chloride which resulted in dramatic changes in the neuronal cytoskeleton even at subtoxic concentrations. Using cultures from mice with red fluorescent protein driven by the tyrosine hydroxylase (TH) promoter, we found that dopaminergic neurons were more susceptible to manganese toxicity. To understand the vulnerability of dopaminergic cells to chronic manganese exposure, mice were given i.p. injections of MnCl2 for 30 days. We observed a 20% reduction in TH-positive neurons in the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as evidenced by the loss of glutamic acid decarboxylase 67 in the striatum. These studies suggest that acute manganese exposure induces cytoskeletal dysfunction prior to degeneration and that chronic manganese exposure results in neurochemical dysfunction with overlapping features to PD.

Original languageEnglish (US)
Pages (from-to)378-389
Number of pages12
JournalJournal of Neurochemistry
Volume110
Issue number1
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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Keywords

  • Dopamine
  • Manganese
  • Neurotoxicity
  • Parkinson's disease
  • Striatum
  • Substantia nigra

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Stanwood, G. D., Leitch, D. B., Savchenko, V., Wu, J., Fitsanakis, V. A., Anderson, D. J., Stankowski, J. N., Aschner, M., & McLaughlin, B. (2009). Manganese exposure is cytotoxic and alters dopaminergic and GABAergic neurons within the basal ganglia. Journal of Neurochemistry, 110(1), 378-389. https://doi.org/10.1111/j.1471-4159.2009.06145.x