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.

Keywords: Astrocytes; Corpus striatum; Manganese; Microglia; Neurodegeneration; Neuropathology.

Figure 1. Gross and immunohistochemical sections

A, representative coronal section demonstrating the basal ganglia level where histological sampling was undertaken (C- Caudate, P-Putamen, IC- Internal capsule, GPe- Globus pallidus externa, GPi- Globus pallidus interna). B, representative high power (40×) GFAP-stained sections from an Mn exposed subject (black arrows demonstrate representative immunoreactive astrocytes, blue arrowheads show non-immunoreactive neurons, red arrowheads show non-immunoreactive oligodendrocytes). C, representative high power (40×) MAP2-stained sections from an Mn exposed subject, (black arrows demonstrate representative immunoreactive neurons, blue arrowheads show non-immunoreactive astrocytes, red arrowheads show non-immunoreactive oligodendrocytes). D, representative high power (40×) CD68-stained sections from an Mn exposed subject (black arrows demonstrate representative immunoreactive microglia).