Manganese Neurotoxicity

A bstract : Manganese is an essential trace element and it is required for many ubiquitous enzymatic reactions. While manganese deficiency rarely occurs in humans, manganese toxicity is known to occur in certain occupational settings through inhalation of manganese‐containing dust. The brain is particularly susceptible to this excess manganese, and accumulation there can cause a neurodegenerative disorder known as manganism. Characteristics of this disease are described as Parkinson‐like symptoms. The similarities between the two disorders can be partially explained by the fact that the basal ganglia accumulate most of the excess manganese compared with other brain regions in manganism, and dysfunction in the basal ganglia is also the etiology of Parkinson's disease. It has been proposed that populations already at heightened risk for neurodegeneration may also be more susceptible to manganese neurotoxicity, which highlights the importance of investigating the human health effects of using the controversial compound, methylcyclopentadienyl manganese tricarbonyl (MMT), in gasoline to increase octane. The mechanisms by which increased manganese levels can cause neuronal dysfunction and death are yet to be elucidated. However, oxidative stress generated through mitochondrial perturbation may be a key event in the demise of the affected central nervous system cells. Our studies with primary astrocyte cultures have revealed that they are a critical component in the battery of defenses against manganese‐induced neurotoxicity. Additionally, evidence for the role of oxidative stress in the progression of manganism is reviewed here.