Journal
NEUROTOXICOLOGY
Volume 45, Issue -, Pages 260-266Publisher
ELSEVIER
DOI: 10.1016/j.neuro.2013.12.008
Keywords
Neuropathology; Manganese; Neurodegeneration; Corpus striatum; Astrocytes; Microglia
Categories
Funding
- National Institute for Environmental Health Sciences (NIEHS) [R01ES019277-02S1]
- NIEHS [R21ES17504, R01ES019277, K24 ES017765, P42ES004696]
- St. Louis Chapter of the American Parkinson Disease Association
- NIH [K23 ES021444-01]
- NIEHS, National MS society
- NIH Grant [UL1 RR024992]
- Michael J. Fox Foundation, NINDS Grant [5T32NS007205-27]
- NCRR0
- NIH Roadmap for Medical Research Grant [UL1 RR024992, UL1 TR000448]
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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. (C) 2014 Elsevier Inc. All rights reserved.
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