Parkinsons Disease

Study Bolsters Link

between Pesticides

People who have been exposed to pesticides are 70 percent more likely to develop Parkinsons disease than those who haven't, according to a new study.

The results suggest that any pesticide exposure, whether occupationally related or not, will increase a person's risk of the disease.

This means that using pesticides in the home or garden may have similarly harmful effects as working with the chemicals on a farm or as a pest controller.

The research, published in the July issue of Annals of Neurology, provides the strongest evidence to date of the link between pesticide exposure and Parkinsons.

The study included over 143,000 men and women who completed extensive lifestyle questionnaires beginning in 1982, and follow-up surveys through 2001.

All subjects were symptom-free at the beginning of the project, when they were asked about their occupation and exposure to potentially hazardous materials.

Since then, 413 of them have developed confirmed cases of Parkinsons, with a greater incidence of the disease in those who spent time around pesticides.

"Low-dose pesticide exposure was associated with a significant increase in risk for Parkinsons disease," says lead author Alberto Ascherio of the Harvard School for Public Health.

"I think this is one reason to be careful about using pesticides in general."

Although the causes of Parkinson's are not well understood, it has long been suspected that environmental factors play a large role.

Animal studies have shown that chemical compounds commonly used as pesticides can cause a degeneration of dopamine-producing neurons.

In Parkinsons, a shortage of dopamine causes the disease's characteristic motor abnormalities, including muscle tremors and muscle rigidity.

Previous small-scale human studies had suggested a link between pesticides and Parkinsons, but this new study is the first to establish a clear correlation in a large patient population.

The researchers also looked for links between Parkinsons and other environmental contaminants, including asbestos, coal dust, exhaust, formaldehyde and radioactive material.

They found no correlation between the disease and any of the materials besides pesticides, however.

Because of the design of the questionnaires, the study was not able to determine how the frequency, duration, or intensity of pesticide exposure affected the incidence of Parkinsons.

The next step, according to Ascherio, is to figure out which class of chemicals is actually causing the disease, so that people can reduce their exposure.

Pesticides and Parkinson's Over one million Americans suffer from Parkinson’s disease, the cause of which is largely unknown.

Although mutations in several proteins can lead to inherited forms of the disease, nobody knows what triggers the overwhelming number of sporadic cases.

Now researchers from Emory University in Georgia have shown that the pesticide rotenone causes Parkinson’s symptoms in rats by inhibiting an enzyme complex in the respiratory chain of their mitochondria.

Parkinson’s normally starts late in life and leads to progressive muscle stiffness, tremors and slowness of movement.

These symptoms arise because nerve cells producing the neurotransmitter dopamine, located in an area of the brain known as the substantia nigra, slowly die.

Typically, fibrillar protein inclusions, so-called Lewy bodies, form in the cytoplasm.

In the December issue of Nature Neuroscience, the researchers report that when they continuously infused rats with low doses of rotenone, a plant-derived pesticide used as an insecticide and in fish control, the animals developed behavioral symptoms of Parkinson’s.

Also, their dopaminergic neurons died, and some contained inclusions similar to Lewy bodies.

Rotenone easily crosses the cell membrane and inhibits the NADH dehydrogenase complex (complex I) in the respiratory chain of the mitochondria. Nevertheless, the researchers found that it does not significantly affect respiration in the brain. Instead it probably creates free radicals that cause oxidative damage, leading to protein inclusions and cell death.

Dopaminergic nerve cells may in fact be especially sensitive to oxidative stress, which is why only they succumb.

These results don't yet prove that Parkinson's disease in humans can result from long-term exposure to low levels of rotenone or similar pesticides.

But epidemiological studies have identified pesticides as a risk factor for the disease.

Thus, environmental substances that inhibit complex I of mitochondria may represent a major cause of Parkinson’s.

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