Fungicidal chemicals routinely used on crops, especially leafy greens, produce gene expression changes in mice that are very similar to those in people with autism and neurodegenerative conditions, including Alzheimer’s disease and Huntington’s disease.
The findings, published in the journal Nature Communications, describe a new way to home in on chemicals that have the potential to affect brain functions.
Mark Zylka, senior author of the study and associate professor of cell biology and physiology at UNC School of Medicine, and his team exposed mouse neurons to approximately 300 different chemicals. Then the researchers sequenced RNA from these neurons to find out which genes were misregulated when compared to untreated neurons.
This work created hundreds of data sets of gene expression; genes give rise to products, including proteins or RNA.
Zylka’s team then used computer programs to deduce which chemicals caused gene expression changes that were similar to each other.
“Based on RNA sequencing, we describe six groups of chemicals,” Zylka says. “We found that chemicals within each group altered expression in a common manner. One of these groups of chemicals altered the levels of many of the same genes that are altered in the brains of people with autism or Alzheimer’s disease.”
More Research Needed
Chemicals in this group included the pesticides rotenone, pyridaben, and fenpyroximate, and a new class of fungicides that includes pyraclostrobin, trifloxystrobin, fenamidone, and famoxadone. Azoxystrobin, fluoxastrobin, and kresoxim-methyl are also in this fungicide class.
“We cannot say that these chemicals cause these conditions in people,” Zylka cautions. “Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain.”
The group found that these chemicals reduced the expression of genes involved in synaptic transmission—the connections important for communication between neurons. If these genes are not expressed properly, then our brains cannot function normally.
Also, these chemicals caused an elevated expression of genes associated with inflammation in the nervous system. This so-called neuroinflammation is commonly seen in autism and neurodegenerative conditions.
The researchers also found that these chemicals stimulated the production of free radicals—particles that can damage the basic building blocks of cells and that have been implicated in a number of brain diseases. The chemicals also disrupted neuron microtubules.
“Disrupting microtubules affects the function of synapses in mature neurons and can impair the movement of cells as the brain develops,” Zylka says. “We know that deficits in neuron migration can lead to neurodevelopmental abnormalities. We have not yet evaluated whether these chemicals impair brain development in animal models or people.”
Fungicide on Lettuce
Zylka’s group also analyzed information from the US Geological Survey, which monitors countywide pesticide usage, as well as the Food and Drug Administration and the US Department of Agriculture, which test foodstuffs yearly for pesticide residues.
Of the chemicals Zylka’s team studied, only the usage of pyridaben has decreased since 2000. Rotenone use has remained the same since 2000. However, the use of all the fungicides in this group has increased dramatically over the past decade.
Indeed, a study from the Environmental Protection Agency found that pyraclostrobin is found on foods at levels that could potentially affect human biology, and another study linked pyraclostrobin usage to honeybee colony collapse disorder.
The pesticide rotenone was previously implicated in Parkinson’s disease through replicated animal experiments and through human epidemiological studies. A separate 2015 UNC study found that Parkinson’s disease is much more common in older adults with autism than in older adults without autism.
Previous work has also shown that a single dose of the fungicide trifloxystrobin reduced motor activity for several hours in female rats and for days in male rats. Disrupted motor function is a common symptom of Parkinson’s disease and other neurological disorders.
The related fungicide picoxystrobin impaired motor activity in rats at the lowest dose tested.
“The real tough question is: if you eat fruits, vegetables, or cereals that contain these chemicals, do they get into your blood stream and at what concentration? That information doesn’t exist.”
Also, given their presence on a variety of foodstuffs, might long term exposure to these chemicals—even at low doses—have a cumulative effect on the brain?
Zylka notes that conventionally grown leafy green vegetables such as lettuce, spinach, and kale have the highest levels of these fungicides. But due to each chemical’s effectiveness at reducing fungal blights and rust, crop yields have increased and farmers are expanding their use of these chemicals to include many additional types of food crops.
Zylka’s team hopes their research will encourage other scientists and regulatory agencies to take a closer look at these fungicides and follow up with epidemiological studies.
“Virtually nothing is known about how these chemicals impact the developing or adult brain,” Zylka says. “Yet these chemicals are being used at increasing levels on many of the foods we eat.”
Brandon L. Pearson, Jeremy M. Simon, Eric S. McCoy, Gabriela Salazar, Giulia Fragola & Mark J. Zylka Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration Nature Communications 7, Article number: 11173 doi:10.1038/ncomms11173
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