8292560 Neuropathological effects of manganese exposure in South African mineworkers

<h3>Background</h3> Chronic exposure to manganese (Mn) has been associated with neurological dysfunction, but the neuropathological effects are not well understood. South Africa has 80% of the world’s Mn reserves and a large mining workforce exposed to Mn. <h3>Objectives</h3> We investigated differences in cell counts in the brains of deceased South African Mn-exposed and -unexposed mineworkers, and associations between cell counts and duration of exposure. <h3>Methods</h3> Postmortem brain tissue from 35 mineworkers from the Northern Cape province of South Africa (23 Mn-exposed, 12 -unexposed) was obtained with next-of-kin consent. Astrocytes and neurons in striatal regions (caudate, putamen, globus pallidus internus, and globus pallidus externus) were quantified using validated, reproducible stereological methods. Multiple linear regression analysis was used to compare cell counts between exposed and non-exposed mineworkers, and to assess the association between duration of Mn exposure and cell counts. <h3>Results</h3> Median age at death was 53 and 60 years for Mn-exposed and -unexposed mineworkers, respectively. Duration of employment (Mn exposure) ranged from 0.4 to 39.7 years (median 15.7 years) in the Mn mine workers. Astrocyte counts were significantly lower in the caudate of Mn-exposed than -unexposed mineworkers (p=0.025), with inverse associations between duration of Mn exposure and astrocyte counts. Neuronal counts showed similar trends. There was a strong inverse association between duration of Mn exposure and astrocyte count in the caudate (p=0.005) and a trend toward an inverse association in the putamen, globus pallidus internus, and globus pallidus externus. There was a strong trend toward lower neuronal cell count in the caudate, but not in the other striatal regions. <h3>Conclusion</h3> Mn exposure appears to be associated with region-specific reduced astrocyte and neuronal cell counts. These findings support the neurotoxic effects of occupational Mn exposure.