Researchers discovered that frequently used fungicides – chemicals used commercially to get rid of fungi in crops – cause the same kind of changes in gene expression as scientists report are present in patients with neurodegenerative diseases, such as Huntington’s and Alzheimer’s diseases, as well as autism.
The study, “Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration,” was published in the journal Nature Communications.
Epidemiological studies have previously linked certain chemicals to neurodegenerative diseases. The design of these studies, however, only allows finding a link, without any possibility to prove that a chemical actually drives disease development.
To get more hands on proof, scientists at the University of North Carolina School of Medicine, led by associate professor of cell biology and physiology Mark Zylka, cultured mouse neurons in the lab, and exposed them to hundreds of different chemicals. They then analyzed the gene expression of the cells, comparing treated and untreated neurons.
Ending up with huge data sets, the team then made use of advanced computing software to identify chemicals that induced similar types of changes.
“Based on RNA sequencing, we describe six groups of chemicals,” Zylka said in a press release. “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.”
The research group included the pesticides rotenone, pyridaben, and fenpyroximate, and a new class of fungicides including the substances pyraclostrobin, trifloxystrobin, fenamidone, and famoxadone. Azoxystrobin, fluoxastrobin, and kresoxim-methyl are other fungicides that belong to this class.
While the study provides more evidence that the chemicals might lead to changes involved in disease, they do not in any way constitute the final proof.
“We cannot say that these chemicals cause these conditions in people,” Zylka cautioned. “Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain.”
The changes in the neurons that the team observed were linked to synaptic transmission – the process of neuronal communication – a process without which we simply cannot function. The investigated chemicals also induced inflammatory changes in the nerves, another common hallmark of neurodegeneration.
Other chemical-induced changes that the team detected involved free radical production, and disruption of neuron microtubules – structures within nerve cells crucial for proper function of synapses. Microtubules are also involved in the migration of cells in the developing brain.
“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,” Zylka explained.
Jeannie T. Lee, professor of genetics at Harvard Medical School and Massachusetts General Hospital, who was not involved in this research, said, “This is a very important study that should serve as a wake-up call to regulatory agencies and the general medical community. The work is timely and has wide-ranging implications not only for diseases like autism, Parkinson’s, and cancer but also for the health of future generations. I suspect that a number of these chemicals will turn out to have effects on transgenerational inheritance.”
To check if the results have any practical implications, the researchers also analyzed data from the U.S. Geological Survey, the Food and Drug Administration and the U.S. Department of agriculture. The data, reporting on pesticide use and pesticide residues on foodstuffs, showed that the use of only one chemical had decreased since 2000 – h.
While rotenone use was stable over the same period, the use of all the fungicides in this group had skyrocketed. This was confirmed in a recent study by the Environmental Protection Agency, showing that levels of the antifungal pyraclostrobin on foods were high enough to interfere with human biology. Another study linked the chemical to the collapse of honeybee colonies.
Suspicions that chemical exposure might be linked to the development of neurodegenerative diseases is nothing new. Rotenone has been tied to Parkinson’s disease in animal experiments and researchers have shown that the fungicide trifloxystrobin decreased motor activity in rats, as did the related fungicide picoxystrobin – at the lowest dose investigated.
Zylka added, “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.”
Scientists also worry that long-term exposure from the chemicals on food might have a cumulative effect in the brain.
Traditionally, these fungicides have been used mostly on leafy green vegetables such as lettuce, spinach, and kale, which also present with the highest levels when analyzed. Since the fungicides are so effective, leading to increased crops, farmers now expand their use of these chemicals, treating many more foodstuffs.
The team hopes their findings will become an eye opener for other scientists and regulatory agencies, spurring more research into the effects of the fungicides.
“Virtually nothing is known about how these chemicals impact the developing or adult brain,” Zylka said. “Yet these chemicals are being used at increasing levels on many of the foods we eat.”
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