Long-term residential exposure to chlorpyrifos, a pesticide used in agriculture for decades, was associated with more than twice the risk of Parkinson’s disease in a UCLA Health study. Experiments in mice and zebrafish also suggested how the chemical may damage the brain: by disrupting autophagy, the cellular process that removes damaged proteins and other waste from neurons.
Chlorpyrifos exposure and Parkinson’s disease risk
Parkinson’s disease affects approximately 1 million Americans. This progressive neurological condition damages brain cells involved in movement and can cause tremors, muscle stiffness, slowed movements and problems with coordination.
A defining feature of Parkinson’s disease is the loss of neurons that produce dopamine. This chemical messenger allows nerve cells to communicate and helps the brain coordinate smooth, controlled movements. As dopamine levels fall, the brain becomes less able to regulate movement.
Genetic factors can influence who develops Parkinson’s disease, but researchers are increasingly studying environmental exposures that may also contribute to the condition. Pesticides are of particular interest because some chemicals used to control insects and other agricultural pests can interfere with biological processes in the nervous system.
Chlorpyrifos has been widely used in agriculture for decades. Its residential use was banned in the United States in 2001, and agricultural uses faced additional restrictions in 2021. The pesticide is still used on many crops in the United States and remains widely used in other countries.
Understanding its potential long-term effects is important because exposure may occur years before Parkinson’s symptoms appear. Identifying specific chemicals associated with the disease could help researchers develop prevention strategies and determine whether people with past exposure might benefit from additional neurological monitoring.
Human study found more than double the risk
UCLA scientists examined data from 829 people diagnosed with Parkinson’s disease and 824 people without the condition. All participants were enrolled in the university’s long-term Parkinson’s Disease Environment and Genetics Study, which investigates how environmental exposures and genetic factors affect Parkinson’s risk.
The researchers combined California’s detailed pesticide-application records with participants’ residential and work-address histories. This allowed them to estimate how much chlorpyrifos each person may have encountered over time based on where they lived or worked.
People with long-term residential exposure to chlorpyrifos had more than 2.5 times the risk of developing Parkinson’s disease compared with people without exposure.
Because this population analysis could not prove that chlorpyrifos directly caused Parkinson’s disease, the researchers conducted additional laboratory experiments to determine whether the pesticide could produce brain changes associated with the condition.
Experiments revealed changes in brain cells
The research team exposed mice to chlorpyrifos in aerosol form for 11 weeks. The inhalation method was intended to resemble a common way people may encounter pesticides in the environment.
The exposed mice developed movement difficulties and lost neurons involved in dopamine production. The finding was significant because the degeneration of these nerve cells is a central feature of Parkinson’s disease.
The researchers also observed inflammation and abnormal accumulation of alpha-synuclein in the animals’ brains.
Under normal conditions, α-synuclein is present in neurons and plays a role in neuronal function. However, the protein can form abnormal clumps and is closely associated with Parkinson’s disease. These deposits are a major focus of research into why certain brain cells deteriorate over time.
Together, the findings indicate that chlorpyrifos exposure can reproduce several key features of Parkinson’s disease in laboratory animals, strengthening the biological evidence supporting the human population findings.
Chlorpyrifos disrupted the brain’s cellular cleanup system
The researchers then used zebrafish to investigate how chlorpyrifos harms neurons. These small fish are widely used in neuroscience because they allow scientists to study biological processes involved in the development and survival of nerve cells.
The experiments pointed to disruption of autophagy, a natural cell-maintenance process that removes damaged proteins and other unwanted substances.
Autophagy functions like a cellular recycling system. Cells use it to break down worn or defective components and prevent potentially harmful material from accumulating. The process is especially important for neurons, many of which must function throughout a person’s life.
When chlorpyrifos interfered with autophagy, damaged substances accumulated within neurons and contributed to their deterioration.
The researchers also found that restoring the cell’s cleanup process or removing the synuclein protein protected neurons from damage in their experiments. This suggests that some harmful pesticide effects may depend on biological pathways that could potentially be targeted by future treatments.
Potential implications for prevention and treatment
The findings raise the possibility of developing treatments that strengthen cellular cleanup mechanisms and protect vulnerable neurons. Such treatments could eventually be useful for people exposed to chlorpyrifos or to other pesticides that interfere with similar processes.
However, these protective effects have so far been demonstrated only in laboratory models. Further research is needed to determine whether enhancing autophagy can prevent or reduce pesticide-related brain damage in humans.
Scientists also want to determine whether other commonly used pesticides affect the same cellular mechanisms. Although chlorpyrifos use has declined in the United States, many people were exposed before restrictions took effect, and related pesticides remain widely used.
The results could also help identify people with a history of substantial pesticide exposure who may benefit from closer neurological monitoring. Early recognition of changes in brain function could become increasingly important as researchers pursue ways to slow or prevent Parkinson’s disease progression.
Dr. Jeff Bronstein, a professor of neurology at UCLA Health and the study’s lead author, emphasized the importance of identifying specific chemicals rather than treating all pesticides as one category.
“This study demonstrated that chlorpyrifos is not just a common type of pesticide, but a specific environmental risk factor for Parkinson’s disease,” Bronstein said.
“By demonstrating the biological mechanism in an animal model, we have demonstrated that this association is likely to be causal. The finding that autophagy dysfunction causes neurotoxicity also leads us to potential therapeutic strategies to protect vulnerable brain cells.”
Source: www.sciencedaily.com
