Pathophysiology of manganese-associated neurotoxicity

Brad A. Racette, Michael Aschner, Tomas R. Guilarte, Ulrike Dydak, Susan R. Criswell, Wei Zheng

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide (Couper, 1837). Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms (Rodier, 1955). Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures (Rodier, 1955; Hobson et al., 2011). The clinical syndrome associated with Mn neurotoxicity has been called manganism.Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers (Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011). Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers (Huang et al., 2003), many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system (Jankovic, 2005).The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from Caenorhabditis elegans to humans. Dr. Aschner's presentation discussed mechanisms of dopaminergic neuronal toxicity in C. elegans and demonstrates a compelling potential role of Mn in dopaminergic degeneration. Dr. Guilarte's experimental, non-human primate model of Mn neurotoxicity suggests that Mn decreases dopamine release in the brain without loss of neuronal integrity markers, including dopamine. Dr. Racette's presentation demonstrates a unique pattern of dopaminergic dysfunction in active welders with chronic exposure to Mn containing welding fumes. Finally, Dr. Dydak presented novel magnetic resonance (MR) spectroscopy data in Mn exposed smelter workers and demonstrated abnormalities in the thalamus and frontal cortex for those workers. This symposium provided some converging evidence of the potential neurotoxic impact of Mn on the dopaminergic system and challenged existing paradigms on the pathophysiology of Mn in the central nervous system.

Original languageEnglish (US)
Pages (from-to)881-886
Number of pages6
JournalNeuroToxicology
Volume33
Issue number4
DOIs
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Manganese
Dopamine
Welding
Caenorhabditis elegans
Parkinsonian Disorders
Nervous System Diseases
Manganese mines
Magnetic resonance spectroscopy
Fumes
Hypokinesia
Iron and steel industry
Neurotoxins
Neurology
Dystonia
Steel
Terminology
Frontal Lobe
Occupational Exposure
Basal Ganglia
Thalamus

Keywords

  • Manganese
  • MRI
  • Parkinsonism
  • PET

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Racette, B. A., Aschner, M., Guilarte, T. R., Dydak, U., Criswell, S. R., & Zheng, W. (2012). Pathophysiology of manganese-associated neurotoxicity. NeuroToxicology, 33(4), 881-886. https://doi.org/10.1016/j.neuro.2011.12.010

Pathophysiology of manganese-associated neurotoxicity. / Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei.

In: NeuroToxicology, Vol. 33, No. 4, 08.2012, p. 881-886.

Research output: Contribution to journalArticle

Racette, BA, Aschner, M, Guilarte, TR, Dydak, U, Criswell, SR & Zheng, W 2012, 'Pathophysiology of manganese-associated neurotoxicity', NeuroToxicology, vol. 33, no. 4, pp. 881-886. https://doi.org/10.1016/j.neuro.2011.12.010
Racette BA, Aschner M, Guilarte TR, Dydak U, Criswell SR, Zheng W. Pathophysiology of manganese-associated neurotoxicity. NeuroToxicology. 2012 Aug;33(4):881-886. https://doi.org/10.1016/j.neuro.2011.12.010
Racette, Brad A. ; Aschner, Michael ; Guilarte, Tomas R. ; Dydak, Ulrike ; Criswell, Susan R. ; Zheng, Wei. / Pathophysiology of manganese-associated neurotoxicity. In: NeuroToxicology. 2012 ; Vol. 33, No. 4. pp. 881-886.
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