Chapter 18: A Decade of Studies on Manganese Neurotoxicity in Non-Human Primates: Novel Findings and Future Directions

Manganese (Mn) is an essential element required for human health because it serves a cofactor function for a number of enzymes in humans. Despite its physiological function, Mn is a double-edged sword in that increased concentrations of Mn in the brain, above those needed for physiological functions, produce a neurological syndrome with behavioral, psychiatric and motor function deficits that are of great concern for human health. We came to study Mn neurotoxicity in non-human primates at a time when there was a great deal of debate and uncertainty in the scientific literature about the role of Mn in idiopathic Parkinson's disease, and its underlying mechanism of toxicity in dopaminergic neurons. There was emerging evidence from human studies that exposure to excess levels of Mn resulted in neuropsychiatric symptoms and cognitive function deficits. In this chapter, I will describe the beginning of our studies on Mn neurotoxicity in non-human primates, what we have discovered, and the new direction that the research has taken. It is important to emphasize that the studies have been a collective effort from many colleagues and collaborators in many departments and research institutions. Only using this transdisciplinary approach could we have accomplished the science that we are doing today and the important findings that are defining the role of Mn in human health and disease.