Scientists say rat study provides intriguing clues to understanding Parkinson's disease

Rotenone, an organic product made from extracts of tropical plants, is widely used as an agricultural pesticide and to kill unwanted fish in reservoirs

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ATLANTA, Georgia -- New research on rats has given scientists intriguing clues suggesting that long-term exposure to environmental toxins might contribute to the development of Parkinson's disease.

More than 1 million Americans suffer from Parkinson's disease. About 1 percent of people older than 65 are Parkinson's victims, suffering tremors such as facial tics and shaking hands. Advanced symptoms include a shuffling gait, speech difficulties and muscle weakness.

Why Parkinson's disease strikes remains a mystery in the majority of cases.

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Now, scientists may be closing in on a long-standing hunch that environmental toxins trigger the disease. In experiments on rats, they've identified a toxin -- Rotenone -- that produces debilitating Parkinson's-like symptoms.

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.

Over a period of weeks, researchers at Emory University in Atlanta, Georgia, gave rats continuous but low doses of Rotenone. Neurologists implanted tiny pumps in the rats to continuously administer Rotenone through the jugular vein for as long as five weeks.

They chose Rotenone because it was known to affect the so-called "power plants" inside cells, called mitochondria, said Dr. Tim Greenamyre, a neurologist in Emory University's medical school.

What happened raised eyebrows. Half the rats gradually displayed Parkinson's-like symptoms, growing slow and stiff, Greenamyre said.

When the rats' brains were examined, researchers found that large numbers of dopamine-producing cells had died or were damaged. In Parkinson's victims, muscle control ebbs as brain cells in a region called the substantial nigra produce less dopamine, a hormone vital to normal nerve function.

Cells in the rats' brains also showed fibrous protein deposits that closely resemble Lewy bodies -- deposits found in brain cells of Parkinson's patients.

"Some of (the rats) even had a little tremor, which is very unusual. We hadn't seen that in a rat before," Greenamyre said. "Together, it's what you see in Parkinson's."

"We don't know that this particular chemical (Rotenone) is a culprit in Parkinson's disease," Greenamyre said. "But I think chemicals like this that act in the same way, and have the same bad effects on mitochondria, could be a major cause of Parkinson's disease."

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," Greenamyre said. "Whether the pesticide would have the same effect in people via normal routes of exposure is not clear."

Scientists say the Emory experiment's results strongly indicate what researchers have suspected for several years -- that the most common form of Parkinson's disease might result from toxins in the environment.

The Parkinson's study, the results of which were published in the December issue of Nature Neuroscience, does not prove that 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 disease.

"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, California, who was not involved in the study. "It is not direct evidence that Rotenone causes Parkinson's. The whole puzzle hasn't come together."

Current drug and surgical therapies for Parkinson's disease tend 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.

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.

Researchers at Emory University in Atlanta administered rotenone to laboratory animals in an effort to better understand Parkinson's disease

People most frequently would be exposed to rotenone by ingesting residue in food or by handling the compound.

How Rotenone might have triggered the changes in the rats is unclear. But University of Pennsylvania researchers Benoit I. Giasson and Virginia M.-Y. Lee, who reviewed the Emory experiment, suggest the pesticide might target the mitochondria.

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.

Pesticide industry representatives contacted by CNN said they would have to evaluate the study before commenting.

CNN Medical Correspondent Rhonda Rowland and The Associated Press contributed to this report.

The Associated Press contributed to this report.

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