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Fungicide linked to neurodegenerative conditions

The 31 March issue of Science Daily reports that scientists at the University of North Carolina School of Medicine have found a class of commonly used fungicides that produce gene expression changes similar to those in people with autism and neurodegenerative conditions.

Mark Zylka, PhD, senior author of the study and associate professor of cell biology and physiology at UNC, 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. Zylka’s team used computer programs to deduce which chemicals caused gene expression changes that were similar to each other.

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.

Zylka and his 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.

Zylka’s group also analyzed information from the U.S. Geological Survey, which monitors countywide pesticide usage, as well as the Food and Drug Administration and the U.S. 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.

Journal Reference:

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, 2016; 7: 11173 DOI: 10.1038/ncomms11173

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