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Researchers at UCLA Health and Harvard have identified 10 pesticides that significantly damaged nerve cells involved in the development of Parkinson’s disease, providing new clues about the role of environmental toxins in the disease.
While environmental factors such as exposure to pesticides have long been associated with Parkinson’s disease, it has been difficult to identify which pesticides may increase the risk of developing the neurodegenerative disorder. Only in California, the nation’s largest agricultural producer and exporter, are there nearly 14,000 insecticidal products with more than 1,000 active ingredients registered for use.
Through a new coupling of epidemiology and toxicity screening that tapped California’s extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons. Neurons play a major role in voluntary movement, and the death of these neurons is the hallmark of Parkinson’s disease.
Furthermore, the researchers found that combined exposures to pesticides that are commonly used in combinations in cotton cultivation were more toxic than any single insecticide in that combination.
For this study, published May 16 in the Nature CommunicationsUCLA researchers examined decades-old exposure histories to 288 pesticides among Central Valley patients with Parkinson’s disease who participated in previous studies. The researchers were able to determine each person’s long-term exposure and then, using what they called a pesticide-level association analysis, tested each pesticide individually for association with Parkinson’s disease. Through this untargeted screen, the researchers identified 53 insecticides that appeared to be involved in Parkinson’s disease—most of which had not been previously studied for a possible link and are still in use.
These findings have been shared for laboratory analysis led by Richard Krolewski, MD, PhD, instructor in neurology at Harvard University and a neurologist at Brigham and Women’s Hospital. He tested the toxicity of most of those pesticides in dopaminergic neurons that have been derived from Parkinson’s patients with what are known as induced pluripotent stem cells, a type of “blank slate” cell that can be reprogrammed into neurons very similar to those lost in disease. Parkinson’s Disease.
The ten pesticides identified as directly toxic to these neurons included: four insecticides (dicofol, endosulfan, nalide, propargyt), three herbicides (dicofol, endothal, trifluralin), and three fungicides (copper sulfate). [basic and pentahydrate] and Volpet). Most pesticides are still used today in the United States.
Aside from their toxicity to dopaminergic neurons, there is little that unites these pesticides. It has a range of types of use, is structurally distinct, and does not share a prior classification of toxicity.
The researchers also tested the toxicity of multiple pesticides that are commonly used on cotton fields around the same time, according to the California Pesticide Database. Combinations containing trifluralin, one of the most popular herbicides in California, have produced the most toxicity. Previous research in the Agricultural Health Study, a large research project involving pesticide applicators, has also implicated it in Parkinson’s disease.
Dr. Kimberly Ball, lead author and assistant professor of neuroscience at UCLA, said the study showed their approach could broadly screen for pesticides implicated in Parkinson’s disease and better understand the strength of these associations.
“We were able to implicate more individual clients than any other study before, and it was done in a completely unbiased way,” said Paul. “When you combine this kind of agnostic examination with a field-to-field model, you can identify which pesticides seem to be very important in disease.”
The researchers next plan to study exposure-related epigenetic and metabolic features using integrative omics to help characterize the biological pathways that are disrupted among Parkinson’s patients exposed to pesticides. More detailed mechanistic studies of the specific neuronal processes affected by pesticides such as trifluralin and copper are also underway at Harvard/Brigham and Women’s Laboratories. Laboratory work focuses on distinct effects on dopaminergic neurons and cortical neurons, which are important for movement and cognitive symptoms of Parkinson’s patients, respectively. The basic science is also expanding to include studies of pesticides on non-neuronal cells in the brain — the glia — to better understand how pesticides affect the function of these critical cells.
Other authors include Edinson Lucumi Moreno, Jacques Blank, Christina M. Holton, Tim Affeldt, Melissa Furlong, Yo-Yo, Miles Cockburn, Laura K. Thompson, Alexander Kramerman, Elizabeth M. Richie Blair, Yu-Jun Lee, and Her B. Patel. and Richard T. Lee, Jeff Bronstein, Lee L. Rubin, Vikram Khurana, and Betty Ritz.
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