South African Research Portfolio

Over 15 years ago, while at the London School of Tropical Medicine and Hygiene, Dr. Brad Racette began to collaborate with Professor Gill Nelson, now at the University of the Witwatersrand in Johannesburg, South Africa. Their collaboration initially focused on creating a brain bank of Mn miners but has expanded to include the impact of environmental Mn on neurologic health in adults and children. Recently, they began new partnerships with investigators in the Agincourt cohort in rural northern South Africa.

Neuropathology of Chronic Mn Exposure

Contributions to Science

In a collaboration with the University of the Witwatersrand in Johannesburg, South Africa, we have developed a neuropathology autopsy research program in South African Mn mineworkers and have collected over 80 brains from deceased miners. Our initial results suggest that Mn mineworkers have lower neuron and astrocyte density and higher microglial density in the striatum. This suggests that Mn may induce a proinflammatory balance in the corpus striatum that ultimately leads to neuronal injury. Although these workers have typical high signal in their basal ganglia on MRI, the Mn concentration is the same in Mn miners as compared to non-Mn miners. These workers demonstrate a similar clinical phenotype to our Mn-exposed welders, associated reductions in quality of life, and a U-shaped dose-response relation between parkinsonism and exposure, consistent with the healthy worker effect.

*Figure 2a. Mn Mine Region in the Northern Cape Province in South Africa*

Figure 2b. Wall of an underground Mn mine in the Norther Cape Province in South Africa

Figures 3a-c. MRI imaging of an ex-vivo Mn miner brain and resultant image

Current Projects

Manganese-Induced Neurotoxic Effects Research in South Africa (MINERS)

R01ES026891 (PI-Racette)

The purpose of this study is to perform neuropathologic stereology studies in deceased Mn miner and non-Mn miner brains to investigate the relationship between astrocyte, neuron, and microglial cell counts and Mn exposure. We will also use quantitative immunofluorescence to investigate markers of neuronal health and markers of neurotoxicity in these neuropathologic specimens and will measure tissue metal content to investigate the association with quantitative ex vivo MRI metal sensitive sequences.

Neurologic Health Effects of Environmental Mn Exposures

Our team has recently published several high-impact studies from our SMELTER cohort, in which we developed and validated the tools used to investigate the health effects of environmental Mn in South Africa. We followed these manuscripts with publications, demonstrating an association between environmental Mn exposure and parkinsonian motor outcomes, depression, and cognitive control dysfunction.

Motor and Cognitive Health Outcomes in a Mn-Exposed African Community

R01ES025991 (PI-Racette)

The purpose of this study is to investigate the motor, cognitive, and mood health effects associated with environmental manganese (Mn) exposure from a Mn smelter in a mixed-race South African community.

The effect of exposure to environmental manganese on the neurobehavioral function of children in Meyerton, South Africa

The purpose of this study is to investigate motor and cognitive health outcomes in the Meyerton cohort in relation to cumulative environmental Mn exposure.

Social Determinants of Health and Parkinsonism

We are collaborating with investigators from the Agincourt cohort in rural northern South Africa to investigate the epidemiology of parkinsonism in a population-based rural African population. These studies focus on the impact of life stressors and social determinants of health on age-related parkinsonism.

Africa Initiative Pilot Grant Program (PI-Racette)

The purpose of this pilot grant is to develop preliminary data on the relation between social determinants of health and clinical parkinsonism in the “Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community” cohort, nested within the Agincourt cohort, in the Mpumalanga Province in rural northern South Africa.