Quantitative neuropathology associated with chronic manganese exposure in South African mine workers

Luis F. Gonzalez-Cuyar, Gill Nelson, Susan R. Criswell, Pokuan Ho, Jaymes A. Lonzanida, Harvey Checkoway, Noah Seixas, Benjamin Gelman, Bradley A. Evanoff, Jill Murray, Jing Zhang, Brad A. Racette

Research output: Contribution to journalArticle

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Abstract

Manganese (Mn) is a common neurotoxicant associated with a clinical syndrome that includes signs and symptoms referable to the basal ganglia. Despite many advances in understanding the pathophysiology of Mn neurotoxicity in humans, with molecular and structural imaging techniques, only a few case reports describe the associated pathological findings, and all are in symptomatic subjects exposed to relatively high-level Mn. We performed an exploratory, neurohistopathological study to investigate the changes in the corpus striatum (caudate nucleus, putamen, and globus pallidus) associated with chronic low-level Mn exposure in South African Mn mine workers. Immunohistochemical techniques were used to quantify cell density of neuronal and glial components of the corpus striatum in eight South African Mn mine workers without clinical evidence of a movement disorder and eight age-race-gender matched, non-Mn mine workers. There was higher mean microglia density in Mn mine workers than non-Mn mine workers in the globus pallidus external and internal segments [GPe: 1.33 and 0.87 cells per HPF, respectively (p= 0.064); GPi: 1.37 and 0.99 cells per HPF, respectively (p= 0.250)]. The number of years worked in the Mn mines was significantly correlated with microglial density in the GPi (Spearman's rho 0.886; p= 0.019). The ratio of astrocytes to microglia in each brain region was lower in the Mn mine workers than the non-Mn mine workers in the caudate (7.80 and 14.68; p= 0.025), putamen (7.35 and 11.11; p= 0.117), GPe (10.60 and 16.10; p= 0.091) and GPi (9.56 and 12.42; p= 0.376). Future studies incorporating more detailed occupational exposures in a larger sample of Mn mine workers will be needed to demonstrate an etiologic relationship between Mn exposure and these pathological findings.

Original languageEnglish (US)
Pages (from-to)260-266
Number of pages7
JournalNeuroToxicology
Volume45
DOIs
StatePublished - Dec 1 2014

Fingerprint

Manganese mines
Manganese
Corpus Striatum
Globus Pallidus
Putamen
Microglia
Miners
Neuropathology
Brain
Molecular Imaging
Imaging techniques
Caudate Nucleus
Movement Disorders
Occupational Exposure
Basal Ganglia

Keywords

  • Astrocytes
  • Corpus striatum
  • Manganese
  • Microglia
  • Neurodegeneration
  • Neuropathology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Gonzalez-Cuyar, L. F., Nelson, G., Criswell, S. R., Ho, P., Lonzanida, J. A., Checkoway, H., ... Racette, B. A. (2014). Quantitative neuropathology associated with chronic manganese exposure in South African mine workers. NeuroToxicology, 45, 260-266. https://doi.org/10.1016/j.neuro.2013.12.008

Quantitative neuropathology associated with chronic manganese exposure in South African mine workers. / Gonzalez-Cuyar, Luis F.; Nelson, Gill; Criswell, Susan R.; Ho, Pokuan; Lonzanida, Jaymes A.; Checkoway, Harvey; Seixas, Noah; Gelman, Benjamin; Evanoff, Bradley A.; Murray, Jill; Zhang, Jing; Racette, Brad A.

In: NeuroToxicology, Vol. 45, 01.12.2014, p. 260-266.

Research output: Contribution to journalArticle

Gonzalez-Cuyar, LF, Nelson, G, Criswell, SR, Ho, P, Lonzanida, JA, Checkoway, H, Seixas, N, Gelman, B, Evanoff, BA, Murray, J, Zhang, J & Racette, BA 2014, 'Quantitative neuropathology associated with chronic manganese exposure in South African mine workers', NeuroToxicology, vol. 45, pp. 260-266. https://doi.org/10.1016/j.neuro.2013.12.008
Gonzalez-Cuyar LF, Nelson G, Criswell SR, Ho P, Lonzanida JA, Checkoway H et al. Quantitative neuropathology associated with chronic manganese exposure in South African mine workers. NeuroToxicology. 2014 Dec 1;45:260-266. https://doi.org/10.1016/j.neuro.2013.12.008
Gonzalez-Cuyar, Luis F. ; Nelson, Gill ; Criswell, Susan R. ; Ho, Pokuan ; Lonzanida, Jaymes A. ; Checkoway, Harvey ; Seixas, Noah ; Gelman, Benjamin ; Evanoff, Bradley A. ; Murray, Jill ; Zhang, Jing ; Racette, Brad A. / Quantitative neuropathology associated with chronic manganese exposure in South African mine workers. In: NeuroToxicology. 2014 ; Vol. 45. pp. 260-266.
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abstract = "Manganese (Mn) is a common neurotoxicant associated with a clinical syndrome that includes signs and symptoms referable to the basal ganglia. Despite many advances in understanding the pathophysiology of Mn neurotoxicity in humans, with molecular and structural imaging techniques, only a few case reports describe the associated pathological findings, and all are in symptomatic subjects exposed to relatively high-level Mn. We performed an exploratory, neurohistopathological study to investigate the changes in the corpus striatum (caudate nucleus, putamen, and globus pallidus) associated with chronic low-level Mn exposure in South African Mn mine workers. Immunohistochemical techniques were used to quantify cell density of neuronal and glial components of the corpus striatum in eight South African Mn mine workers without clinical evidence of a movement disorder and eight age-race-gender matched, non-Mn mine workers. There was higher mean microglia density in Mn mine workers than non-Mn mine workers in the globus pallidus external and internal segments [GPe: 1.33 and 0.87 cells per HPF, respectively (p= 0.064); GPi: 1.37 and 0.99 cells per HPF, respectively (p= 0.250)]. The number of years worked in the Mn mines was significantly correlated with microglial density in the GPi (Spearman's rho 0.886; p= 0.019). The ratio of astrocytes to microglia in each brain region was lower in the Mn mine workers than the non-Mn mine workers in the caudate (7.80 and 14.68; p= 0.025), putamen (7.35 and 11.11; p= 0.117), GPe (10.60 and 16.10; p= 0.091) and GPi (9.56 and 12.42; p= 0.376). Future studies incorporating more detailed occupational exposures in a larger sample of Mn mine workers will be needed to demonstrate an etiologic relationship between Mn exposure and these pathological findings.",
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