Fungicides trigger autism-related gene expression changes in mice

The brain cells of mice exposed to a new class of fungicides showed changes in gene expression similar to those found in individuals with autism, Alzheimer’s disease and other neurological conditions, according to the results of a new study.
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A new class of fungicides led to gene expression changes in mouse brain cells similar to changes seen in people with autism, Alzheimer’s and other neurodegenerative disorders.

While the researchers say the findings – published in Nature Communications – cannot confirm that the chemicals cause such conditions in humans, they believe further investigation is warranted.

The study was conducted by senior author Mark Zylka, PhD, associate professor of cell biology and physiology at the University of North Carolina (UNC) School of Medicine, and colleagues.

To reach their findings, the team exposed the brain cells, or neurons, of mice to around 300 chemicals, including a variety of fungicides.

Fungicides are chemicals that can prevent or kill the growth of fungi, protecting plants and crops from fungi-related damage.

The researchers used RNA sequencing on the mouse neurons in order to pinpoint which genes might be affected by exposure to the chemicals, comparing them with neurons that were not exposed to the chemicals.

Using a series of computer programs, the team was able to establish which chemicals triggered similar changes in gene expression.

Fungicides changed same genes that are altered in some brain disorders

The researchers identified six groups of chemicals that altered gene expression within mouse neurons, including the pesticides rotenone, pyridaben and fenpyroximate, as well as a new class of fungicides called strobilurins.

Strobilurins were only introduced into the US market in the late 1990s. Chemicals in this class include pyraclostrobin, trifloxystrobin, fenamidone and famoxadone.

“We found that chemicals within each group altered expression in a common manner,” says Zylka. “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.”

In detail, the researchers found the chemicals reduced the expression of genes that play a role in brain cell communication, which can interfere with brain functioning. The chemicals also increased expression of genes associated with nervous system inflammation, which is often seen in autism and neurodegenerative disorders.

Furthermore, the team found each group of chemicals boosted the production of free radicals – uncharged molecules that can cause cell damage – and interfered with microtubules within brain cells.

“Disrupting microtubules affects the function of synapses in mature neurons and can impair the movement of cells as the brain develops,” explains Zylka. “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.”

Findings ‘should serve as a wake-up call’

According to Zylka, conventionally grown leafy green vegetables – such as spinach, lettuce and kale – have the greatest exposure to strobilurins, though he notes that the chemicals are increasingly being applied to other food crops because they are so effective at protecting against fungi.

The Environmental Protection Agency (EPA) state that the few human studies of strobilurins to date have shown the chemicals are less toxic than many other fungicides, though they have still been associated with short-term eye irritation, upper respiratory tract irritation, dizziness, weakness, skin redness and chest pain.

However, Zylka notes that previous research on the fungicide trifloxystrobin has shown the chemical hampers the motor function of rats for up to several days – a symptom that is common in Parkinson’s disease and other neurological conditions – while a low dose of the fungicide picoxystrobin has also been linked to impaired motor function in rats.

While the authors cannot confirm that strobilurins have the same effect on human brain cells as those of mice, they stress that this is something that should be investigated in future research.

“Virtually nothing is known about how these chemicals impact the developing or adult brain,” says Zylka. “Yet these chemicals are being used at increasing levels on many of the foods we eat.”

Commenting on the findings, Dr. Jeannie T. Lee, professor of genetics at Harvard Medical School and Massachusetts General Hospital – who was not involved in the study – says the results should “serve as a wake-up call to regulatory agencies and the general medical community,” adding:

“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.”

Last December, Medical News Today reported on a study suggesting a pesticide used in the US until the 1980s – heptachlor epoxide – may be linked to Parkinson’s.

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