Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates

Tomás R. Guilarte, Ming Kai Chen, Jennifer L. McGlothan, Tatyana Verina, Dean F. Wong, Yun Zhou, Mohab Alexander, Charles A. Rohde, Tore Syversen, Emmanuel Decamp, Amy Jo Koser, Stephanie Fritz, Heather Gonczi, David W. Anderson, Jay S. Schneider

Research output: Contribution to journalArticle

Abstract

We tested the hypothesis that movement abnormalities induced by chronic manganese (Mn) exposure are mediated by dysfunction of the nigrostriatal dopamine system in the non-human primate striatum. Motor function and general activity of animals was monitored in parallel with chronic exposure to Mn and Positron Emission Tomography (PET) studies of in vivo dopamine release, dopamine transporters and dopamine receptors in the striatum. Analysis of metal concentrations in whole blood and brain was obtained and post-mortem analysis of brain tissue was used to confirm the in vivo PET findings. Chronic Mn exposure resulted in subtle motor function deficits that were associated with a marked decrease of in vivo dopamine release in the absence of a change in markers of dopamine (DA) terminal integrity or dopamine receptors in the striatum. These alterations in nigrostriatal DA system function were observed at blood Mn concentrations within the upper range of environmental, medical and occupational exposures in humans. These findings show that Mn-exposed non-human primates that exhibit subtle motor function deficits have an apparently intact but dysfunctional nigrostriatal DA system and provide a novel mechanism of Mn effects on the dopaminergic system.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalExperimental Neurology
Volume202
Issue number2
DOIs
StatePublished - Dec 1 2006

Keywords

  • Dopamine release
  • Manganese
  • Motor function
  • Parkinson's disease
  • Positron emission tomography

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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  • Cite this

    Guilarte, T. R., Chen, M. K., McGlothan, J. L., Verina, T., Wong, D. F., Zhou, Y., Alexander, M., Rohde, C. A., Syversen, T., Decamp, E., Koser, A. J., Fritz, S., Gonczi, H., Anderson, D. W., & Schneider, J. S. (2006). Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates. Experimental Neurology, 202(2), 381-390. https://doi.org/10.1016/j.expneurol.2006.06.015