Study: Pesticides May Trigger Parkinson’s

Nov. 6, 2000 -- New research using rats suggests that long-term exposure to a

widely used pesticide kills brain cells and triggers debilitating

physical symptoms associated with Parkinson’s disease.

Scientists say the experiment’s results strongly indicate whatscientists have suspected for several years — that the most commonform of Parkinson’s disease might result from toxins in theenvironment.

The new study, published in the December issue of NatureNeuroscience, 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 arepowerful and should reinvigorate the search for environmentaltoxins that may contribute to Parkinson’s, the most commonneurological disorder after Alzheimer’s.

Evidence of Increased Risk

“This is more evidence that a class of compounds may increasethe risk of developing Parkinson’s,” said J. William Langston,director of the Parkinson’s Institute in Sunnyvale, Calif., who wasnot involved in the study. “It is not direct evidence thatrotenone causes Parkinson’s. The whole puzzle hasn’t cometogether.”

More than a million Americans suffer from Parkinson’s.

Muscle control ebbs as brain cells in a region called thesubstantia nigra produce less dopamine, a hormone vital to normalnerve function. The illness is marked by small tremors, such asfacial tics and shaking hands. Advanced symptoms include ashuffling gait, speech difficulties and muscle weakness.

There is no cure, and current drug and surgical therapies tendsto lose effectiveness over time. New therapies involvingtransplants of stem cells, the body’s master cells from which alltissues grow, have been slowed by federal funding restrictions onexperiments using embryonic tissues.

In about 10 percent of patients, Parkinson’s strikes before age50. These rare cases probably are caused by inherited geneticabnormalities.

However, most patients show their first Parkinson’s symptomsafter age 60. Researchers believe older patients may have sufferedbrain damage from chronic exposure to unspecified toxins. Among thesuspects: pesticides, industrial chemicals and tobacco smoke.

Rotenone for Rats

In the experiment conducted at Emory University in Atlanta,neurologists implanted tiny pumps in the rats to continuouslyadminister low doses of rotenone through the jugular vein for aslong as five weeks.

Rotenone is an organic product made from extracts of tropicalplants. It is widely used as an agricultural pesticide and to killunwanted fish in reservoirs.

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

Scientists acknowledged the pump method used in the experimentdid not duplicate rotenone exposure in the real world, but said itwas a more direct and reliable method for research purposes.

“Rats can be picky about what they eat and they might not likeeating rotenone,” said J. Timothy Greenamyre, the study’s seniorauthor. “Whether the pesticide would have the same effect inpeople via normal routes of exposure is not clear.”

Greenamyre said half of the rats gradually showed Parkinson’ssymptoms.

Examination revealed that large numbers of dopamine-producingcells in the rats’ brains had died or were damaged. In addition,the cells showed fibrous protein deposits that closely resembleLewy bodies, deposits found in brain cells of Parkinson’s patients.

“Together, it’s what you see in Parkinson’s,” Greenamyre said.

Rogue Molecules Released

How rotenone might have triggered these changes in rat isunclear. University of Pennsylvania researchers Benoit I. Giassonand Virginia M.-Y. Lee, who reviewed the Emory experiment, suggestthe pesticide might target the mitochondria, a genetic bundle thatgenerates most of a cell’s energy.

Such damage unleashes rogue molecules known as free radicalsthat wreak havoc in cells. Free radicals have been implicated inmany degenerative diseases.

“Neurons are particularly sensitive,” Giasson and Lee noted.

Greenamyre said future rotenone experiments with rats would testnew drugs aimed at protecting dopamine-producing cells.

In the meantime, he suggested that farmers and public healthagencies reconsider pesticide usage.

“Pesticides are essential for growing crops, but we may need tothink about minimizing their environmental impact,” he said.