Scientists say the experiment's results strongly indicate what scientists have suspected for several years: that the most common form of Parkinson's disease might result from toxins in the environment.
The new study, published in the December issue of Nature Neuroscience, does not prove that the pesticide used in the test, rotenone, causes Parkinson's in humans.
But scientists who reviewed the experiment said the results are powerful and should reinvigorate the search for environmental toxins that may contribute to Parkinson's, the most common neurological disorder after Alzheimer's.
"This is more evidence that a class of compounds may increase the risk of developing Parkinson's," said J. William Langston, director of the Parkinson's Institute in Sunnyvale, Ca., who was not involved in the study. "It is not direct evidence that rotenone causes Parkinson's. The whole puzzle hasn't come together."
More than one million Americans suffer from Parkinson's.
Muscle control ebbs as brain cells in a region called the substantia nigra produce less dopamine, a hormone vital to normal nerve function. The illness is marked by small tremors, such as facial tics and shaking hands. Advanced symptoms include a shuffling gait, speech difficulties and muscle weakness.
There is no cure, and current drug and surgical therapies tends to lose effectiveness over time. New therapies involving transplants of stem cells, the body's master cells from which all tissues grow, have been slowed by federal funding restrictions on experiments using embryonic tissues.
In about 10 percent of patients, Parkinson's strikes before age 50. These rare cases probably are caused by inherited genetic abnormalities.
However, most patients show their first Parkinson's symptoms after age 60. Researchers believe older patients may have suffered brain damage from chronic exposure to unspecified toxins. Among the suspects: pesticides, industrial chemicals and tobacco smoke.
In the experiment conducted at Emory University in Atlanta, neurologists implanted tiny pumps in the rats to continuously administer low doses of rotenone through the jugular vein for as long as five weeks.
Rotenone is an organic product made from extracts of tropical plants. It is widely used as an agricultural pesticide and to kill unwanted fish in reservoirs.
People most frequently would be exposed to rotenone by ingesting residue in food or by handling the compound.
Scientists acknowledged the pump method used in the experiment did not duplicate rotenone exposure in the real world, but said it was a more direct and reliable method for research purposes.
"Rats can be picky about what they eat and they might not like eating rotenone," said J. Timothy Greenamyre, the study's enior author. "Whether the pesticide would have the same effect in people via normal routes of exposure is not clear."
Greenamyre said half of the rats gradually showed Parkinson's symptoms.
Examination revealed that large numbers of dopamine-producing cells in the rats' brains had died or were damaged. In addition, the cells showed fibrous protein deposits that closely resemble Lewy bodies, deposits found in brain cells of Parkinson's patients.
"Together, it's what you see in Parkinson's," Greenamyre said.
How rotenone might have triggered these changes in rat is unclear. University of Pennsylvania researchers Benoit I. Giasson and Virginia M.-Y. Lee, who reviewed the Emory experiment, suggest the pesticide might target the mitochondria, a genetic bundle that generates most of a cell's energy.
Such damage unleashes rogue molecules known as free radicals that wreak havoc in cells. Free radicals have been implicated in many degenerative diseases.
"Neurons are particularly sensitive," Giasson and Lee noted.
Greenamyre said future rotenone experiments with rats would test new drugs aimed at protecting dopamine-producing cells.
In the meantime, he suggested that farmers and public health agencies reconsider pesticide usage.
"Pesticides are essential for growing crops, but we may need to think about minimizing their environmental impact," he said.
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