Manganese exposure may speed the emergence of Parkinson's
disease symptoms, according to new findings in animals
SANTA CRUZ, CA, December 4, 2000 -- A new study suggests that too much
manganese, an essential element required by the body in tiny amounts but
toxic at elevated levels, may contribute to the early development of
Parkinson's disease symptoms in susceptible people. Recent
epidemiological studies have suggested an association between
Parkinson's disease and elevated exposure to manganese. The new study in
animals shows that exposure to low levels of manganese does not directly
contribute to the disease, but affects a different part of the brain in
a way that exacerbates the effects of Parkinson's.
Researchers at the University of California, Santa Cruz,
evaluated the effects of low-level exposure to manganese using rats with
a condition that mimics pre-Parkinsonism, an early stage of the disease
in which no symptoms are apparent. Their findings were published in the
current issue of the scientific journal Neurotoxicology and Teratology.
The study highlights the importance of looking at the effects of
toxic substances on sensitive subsets of the population who may be most
vulnerable, said Donald Smith, an associate professor of environmental
toxicology at UC Santa Cruz and a coauthor of the paper.
"We are concerned about how chronic low-level exposures to toxic
substances may accelerate the emergence of neurodegenerative diseases
like Parkinson's," Smith said.
The possibility that people in the early stages of Parkinsonism
could be especially sensitive to moderately increased levels of
manganese is disturbing for several reasons, he said. Manganese is
ubiquitous in the environment, and its increasing use in industrial
processes may cause some people to take in greater amounts from water,
food, and airborne sources. In addition, increased exposure to airborne
manganese could result from the use of the manganese compound MMT as a
gasoline additive. MMT gained approval for use in the U.S. after its
manufacturer, Ethyl Corporation, sued the Environmental Protection
Agency and won. Currently, none of the major oil refineries are using
MMT, but that could change, Smith noted.
"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 cause more subtle health effectsare not well
known, said Roberto Gwiazda, a research toxicologist at UCSC and
coauthor of the study.
In the new study, rats showed impaired muscle control at
manganese doses much lower than those used in previously published
animal studies of manganese toxicity. But Gwiazda cautioned that the
exposure regimen and route (a series of injections) were not comparable
to typical environmental exposures in humans.
Smith and his coworkers are currently conducting follow-up
studies to determine the effects of different doses of manganese and to
better understand the mechanisms underlying those effects. In addition
to Smith and Gwiazda, the paper is coauthored by Ryan Witholt, who
worked on the project as a UCSC undergraduate researcher.
University of California, Santa Cruz.
--
Judith Richards, London, Ontario, Canada
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Today’s Research...
Tomorrow’s Cure
--
Judith Richards, London, Ontario, Canada
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Today’s Research...
Tomorrow’s Cure
