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Another Link Between Pesticides and Parkinsonís Disease

Scientists have linked yet another pesticide to the development of Parkinson’s disease (PD), according to a new study published in the January 8 issue of the Proceedings of the National Academy of the Sciences. The pesticide, a fungicide called benomyl, may lead to the development of PD by interfering with a crucial enzyme in the brain, researchers say.

Benomyl was widely used in agriculture for 30 years. However, in 2001 the US Environmental Protection Agency banned the fungicide after it caused serious health problems in laboratory animals. Additionally, previous research has shown that benomyl interferes with ALDH (aldehyde dehydrogenase), an enzyme that helps to break down toxic chemicals in the brain including one related to dopamine called DOPAL.

Researchers theorized that benomyl, by blocking this breakdown, might cause a build-up of toxic chemicals in the brain. In turn, this build-up might kill high numbers of dopaminergic neurons, possibly leading to PD. To test this hypothesis, researchers led by Jeff Bronstein, M.D., Ph.D., at the University of California, Los Angeles, studied the effects of benomyl on rat neurons (cultured in the lab) and on neurons of live zebrafish. Zebrafish are commonly used in research because scientists can easily observe their brain cells without harming them.

In addition, the researchers examined pesticide use records from California’s Central Valley to see if people who were exposed to high levels of benomyl were more likely to develop PD.

Results

  • When the researchers treated cell cultures with benomyl, about 24 percent of the dopaminergic neurons died.
  • Benomyl prevented ALDH from breaking down toxic chemicals into their nontoxic forms. Among these toxic chemicals that remained toxic was DOPAL.
  • When the researchers treated zebrafish embryos with benomyl, about 25 percent of their dopaminergic neurons died. In contrast, other types of neurons in the brain were unaffected by the pesticide.
  • Zebrafish treated with benomyl swam half as far as unexposed zebrafish, suggesting that the loss of dopaminergic neurons affected their behavior.
  • In California’s Central Valley, only people exposed to benomyl for their jobs, farmers for example, had an increased risk of developing PD, twice the risk for those exposed to the highest level of pesticides.
  • People who lived near fields sprayed with benomyl did not have an increased risk of PD.

What Does It Mean?

This study adds benomyl to a growing list of pesticides now thought to be associated with some cases of PD. It is important to note that benomyl is no longer used in the United States.

Scientists have known for some time that farm workers who used pesticides, or people who lived or worked near fields where they could inhale drifting pesticides, have an increased risk of PD. Yet how these pesticides could cause the disease has been a mystery.

Now researchers have demonstrated a plausible way in which the pesticide benomyl could lead to PD. They showed that benomyl interferes with the body’s ability to eliminate toxic chemicals in the brain. These toxic chemicals include DOPAL, which when it builds up, can kill dopaminergic neurons, potentially contributing to Parkinson’s disease. The fact that benomyl specifically killed dopaminergic neurons both in the Petri dish and in a live animal strengthens the case that the same chain of events could be occurring in some people exposed to benomyl. However, not every farm worker who has used benomyl has developed PD, suggesting that other genetic or environmental factors may also be contributing to PD development.

The vast majority of PD cases are sporadic, meaning they have no known cause. Growing evidence, obtained from both laboratory experiments and studies of people with the disease, indicates that pesticide exposure may contribute to some, but not all, cases of sporadic PD. Although benomyl has not been used in the US for more than a decade, studies of people with PD in California’s Central Valley, an agricultural region with high pesticide use, suggest that the pesticide has lingering toxic effects.

Better understanding of the mechanism that links benomyl to PD may shed light on the mechanism leading to PD in general. Further research is needed to assess the risk of other pesticides and identify agents that are safe to use with no lingering neurologic toxic effects.

Reference: Fitzmaurice AG, Rhodes SL, Lulla A, Murphy NP, Lam HA, O’Donnell KC, Barnhill L, Casida JE, Cockburn M, Sagasti A, Stahl MC, Maidment NT, Ritz B, Bronstein JM (2013) Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease. Proc Natl Acad Sci USA 110:636–641. DOI: 10.1073/pnas.1220399110 http://dx.doi.org/10.1073/pnas.1220399110.

Learn More

Do you have questions about pesticides and other environmental factors? Browse an article on the topic, "Environmental Factors and Parkinson's: What Have We Learned?" written by Caroline M. Tanner, M.D., Ph.D.

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Source Date: Mar 14 2013