Summary: Researchers have identified 10 pesticides that significantly damage the neurons involved in the development of Parkinson’s disease.
The study used California’s extensive pesticide use database and new testing methods to directly identify the toxicity of pesticides critical to voluntary activity to dopaminergic neurons. The combinations of pesticides used in cotton farming are more harmful than any single pesticide.
This study provides new insight into environmental triggers that may cause Parkinson’s disease.
Key facts:
- The researchers identified 10 pesticides that are directly toxic to dopaminergic neurons, which are critical in voluntary movement and whose death is characteristic of Parkinson’s disease.
- In particular, combinations of pesticides used in cotton farming have been found to be more toxic than any single pesticide.
- Of the 10 pesticides identified as directly toxic to dopaminergic neurons, most are still in use in the United States today.
Source: UCLA
UCLA Health and Harvard researchers have identified 10 pesticides that significantly damage the neurons involved in the development of Parkinson’s disease, providing new clues about the role of environmental toxins.
While environmental factors such as pesticide exposure have been linked to Parkinson’s, it has been difficult to identify which pesticides may pose a risk for the neurodegenerative disorder.
Just in California, the nation’s largest agricultural producer and exporter, there are nearly 14,000 pesticide products with more than 1,000 active ingredients.
Through a new epidemiology and toxicity screening that used California’s extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that are directly toxic to dopaminergic neurons.
Neurons play a key role in voluntary movement, and the death of these neurons is a hallmark of Parkinson’s disease.
The researchers also found that combined exposure to pesticides commonly used in combination in cotton farming was more toxic than any other pesticide in that group.
This study was published on May 16 Natural relationshipsUCLA researchers examined decades of exposure history to 288 Central Valley pesticides in previous studies of Parkinson’s disease patients.
The researchers were able to determine each person’s long-term exposure and then used what they called a pesticide-wide association analysis to separately test the association of each pesticide with Parkinson’s.
From this untargeted screen, researchers identified 53 pesticides that appear to be involved in Parkinson’s—many of which have not previously been studied for possible association and are still in use.
Those results were shared for laboratory testing led by Richard Krolewski, MD, PhD, a professor of neurology at Harvard and a neurologist at Brigham and Women’s Hospital.
He tested the toxicity of most of the antibiotics in dopaminergic neurons cultured from Parkinson’s patients by induced pluripotent stem cells, a type of “blank slate” cell that appears to have been lost. Parkinson’s disease.
The 10 pesticides identified as directly toxic to these neurons include: four insecticides (dicofol, endosulfan, naled, propargit), three herbicides (diquat, endothal, trifluralin) and three fungicides (copper sulfate). [basic and pentahydrate] and Folpet). Most pesticides are still used in the United States.
Apart from the toxicity in dopaminergic neurons, there is little that unites these pesticides. They have different uses, are structurally different, and do not share a prior toxicity classification.
According to the California Pesticide Database, researchers tested the toxicity of several pesticides commonly applied to cotton fields at the same time. Compounds containing trifluralin, one of the most commonly used herbicides in California, produced the highest toxicity.
Previous research on agricultural health research, a major research project involving pesticides; Trifluralin has been introduced in Parkinson’s.
Kimberly Paul, Ph.D., an assistant professor of neurology at UCLA, said the study’s approach could better understand the strength of these associations by screening for pesticides implicated in Parkinson’s disease.
“We were able to define more individual agents than any previous study, and it was done in a completely agnostic way,” Paulus said.
“When you put this type of agnostic testing together with a field-to-bench example, you can identify the antibiotics that seem to be most important to the disease.”
The researchers next plan to study exposure-related epigenetic and metabolomic features using in vitro methods to define which biological pathways are disrupted among Parkinson’s patients with pesticide exposure.
More detailed mechanistic studies of the specific neural processes affected by pesticides such as trifluralin and copper are underway at Harvard/Brigham and Women’s laboratories.
His laboratory work focuses on specific effects on dopamine neurons and cortical neurons, which are important for movement and cognitive symptoms in Parkinson’s patients.
To better understand how pesticides affect the function of these vital cells, basic science is expanding to studies of the non-neuronal cells in the brain – glia – pesticides.
Other authors include Edison Lucumi Moreno, Jack Blank, Christina M. Holton, Tim Ahfeldt, Melissa Furlong, Yu Yu, Miles Cockburn, Laura K. , Richard T. Lee, Jeff Bronstein, Lee L. Rubin, Vikram Khurana, and Beat Ritz.
So Parkinson’s disease research news
Author: Jason Millman.
Source: UCLA
Contact: Jason Millman – UCLA
Image: Image credited to Neuroscience News.
Preliminary study: Open Access.
“An antipsychotic and iPSC dopaminergic neuron screen identifies and categorizes antipsychotics relevant to Parkinson’s disease.” by Richard Krolewski et al. Natural relationships
Draft
An antipsychotic and iPSC dopaminergic neuron screen identifies and categorizes antipsychotics relevant to Parkinson’s disease.
Parkinson’s disease (PD) is a complex neurological disease with an etiology based on genetic susceptibility and environmental factors.
Here, a quantitative epidemiologic study of pesticide exposure and PD on dopaminergic neurons derived from PD patient pluripotent stem cells (iPSCs) was combined with toxicity testing to identify Parkinson’s-related pesticides.
Agricultural records allow for examination of 288 specific pesticides and PD risk in the Total Pesticides Association study. We associate long-term exposure to 53 pesticides with PD and identify shared exposure profiles.
We then employ a live-cell imaging filter that exposes dopaminergic neurons to 39 PD-associated inhibitors. We found 10 pesticides to be directly toxic to these neurons.
Additionally, we examine pesticides commonly used in combination in cotton farming, showing that combined exposure results in greater toxicity than any single pesticide alone. We found that trifluralin is a driver of toxicity for dopaminergic neurons and leads to mitochondrial dysfunction.
Our example may be useful for mechanistically dispersing pesticides implicated in PD risk and guiding agricultural policy.