title: Quantitative neuropathology associated with chronic manganese exposure in South African mine workers.
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.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Washington, School of Medicine, Seattle, WA, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Gonzalez-Cuyar
authors.affiliation: School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.
authors.forename: Gill
authors.initials: G
authors.lastname: Nelson
authors.affiliation: Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Criswell
authors.affiliation: Department of Biology, University of Washington, Seattle, WA, USA.
authors.forename: Pokuan
authors.initials: P
authors.lastname: Ho
authors.affiliation: Department of Biology, University of Washington, Seattle, WA, USA.
authors.forename: Jaymes A
authors.initials: JA
authors.lastname: Lonzanida
authors.affiliation: Department of Environmental and Occupational Health, University of Washington, Seattle, WA, USA; Department of Family Medicine and Preventive Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Checkoway
authors.affiliation: Department of Environmental and Occupational Health, University of Washington, Seattle, WA, USA.
authors.forename: Noah
authors.initials: N
authors.lastname: Seixas
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Department of Neuroscience, University of Texas Medical Branch, Galveston, TX, USA; Department of Cell Biology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Evanoff
authors.affiliation: School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa; National Institute for Occupational Health, National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Jill
authors.initials: J
authors.lastname: Murray
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Washington, School of Medicine, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa; Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address: racetteb@neuro.wustl.edu.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Racette
mesh_terms: D000368:Aged; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008297:Male; D020149:Manganese Poisoning / Q000473:pathology*; D017628:Microglia; D008875:Middle Aged; D008906:Mining; D009784:Occupational Diseases / Q000473:pathology*; D016273:Occupational Exposure; D013019:South Africa
keywords: Astrocytes; Corpus striatum; Manganese; Microglia; Neurodegeneration; Neuropathology