"We need better information about the potential risk to sensitive populations when we make decisions about things like MMT," Smith said.

Parkinson's disease and manganese toxicity seem to affect different parts of the neurological pathway involved in muscle control, he said. In Parkinson's disease, loss of brain cells in a region called the substantia nigra results in reduced production of dopamine, a chemical involved in communication between nerve cells. The substantia nigra is part of the basal ganglia, the brain region responsible for fine muscle control. Other parts of the basal ganglia, including the striatum and globus pallidus, are the targets of manganese toxicity.

"If two areas in the same pathway are weakened, you get an additive impact, and that's what we believe occurred in this experiment," Smith said.

In the experiment, rats were treated with a substance toxic to dopamine-producing nerve cells to induce a pre-Parkinson's condition. The treatment moderately reduced dopamine levels in the substantia nigra region of the rats' brains, but did not cause symptoms detectable in a battery of neurobehavioral tests. This created a condition of pre-Parkinsonism mimicking the early neurodegenerative state in the progression of Parkinson's disease. Treated and untreated rats were then given low doses of manganese.

The manganese had no effect on dopamine levels in the substantia nigra, but caused significant impairment of neurologic functions. Furthermore, some of the neurologic effects of manganese were more pronounced in the rats with pre-Parkinsonism.

The toxic effects of manganese have long been known from studies of miners, steelworkers, and others with high occupational exposures. Chronic overexposure to manganese can lead to a disease known as manganism with symptoms similar to Parkinson's disease. But lower doses of manganese that can c
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Contact: Tim Stephens
stephens@cats.ucsc.edu
831-459-2495
University of California - Santa Cruz
3-Dec-2000