Common Agricultural Chemicals Shown to Change Mice Neurons in Ways Similar to Alzheimer’s Disease

Researchers have identified a group of agricultural chemicals — pesticides and fungicides — that constitute environmental risk factors for neurological and neurodegenerative diseases. A recent study found that a number of these chemicals produce gene expression changes in mouse neurons similar to those observed in people with autism, Alzheimer’s disease, and other conditions.

The paper, “Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration,” was published in Nature Communications.

Retrospective epidemiological studies have linked a number of environmental factors, such as pesticides used in agriculture, to risks of autism and neurodegenerative disease. Such chemicals include pyraclostrobin, which has been found in potentially dangerous levels in food in a study by the U.S. Environmental Protection Agency, the pesticide rotenone, which has been associated with Parkinson’s disease risk in both animal experiments and human epidemiological studies, and the fungicides trifloxystrobin and picoxystrobin, shown to impair motor activity in rats.

Researchers from the University of North Carolina (UNC) School of Medicine exposed cultures of mouse neurons to about 300 different chemicals commonly found in the environment and food, and proceeded to sequence RNA extracted from animals’ neurons to assess gene expression profiles of exposed brain cells. These experiments allowed researchers to identify which chemicals caused changes in gene expression. This included rotenone and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, that produce transcriptional changes in vitro similar to those seen in brain samples from people with autism and neurodegenerative diseases such as Alzheimer’s and Huntington’s. Moreover, these chemicals accounted for the reduced expression of genes involved in synapse transmission, stimulated free radical production, and disrupted microtubules within neurons, impairing cellular movement upon brain development and leading to neuro-developmental abnormalities.

Information from U.S. regulatory agencies was also reviewed, such as the  Geological Survey, Food and Drug Administration and the Department of Agriculture, on the use of specific chemicals, observing that pyridaben use has decreased since 2000 and rotenone use has remained the same. Overall fungicide use has increased over the last decade, mainly due to its effectiveness in reducing fungal invasion in food crops.

The study team hopes these findings will encourage other scientists and regulatory agencies to investigate the consequences of  long-term exposure to the chemicals and their cumulative effects on the brain.

“We cannot say that these chemicals cause these conditions in people,” Dr. Mark Zylka, the study’s senior author and an associate professor of cell biology and physiology at UNC, said in a news release. “Many additional studies will be needed to determine if any of these chemicals represent real risks to the human brain.”

He 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.”