Department of Physiology and Pharmacology, and Interdisciplinary Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Address for correspondence: Michael Aschner, Ph.D., Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083. Voice: 336-716-8530; fax: 336-716-8501. maschner{at}wfubmc.edu
Ann N.Y. Acad. Sci. 1012: 115-128 (2004).
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.
