UNE researcher leads identification of novel biomarker for detection of toxic agricultural pesticide

More than six decades after Rachel Carson’s “Silent Spring” awakened the world to the invisible fallout of industrial pesticides, Carson’s warnings about the effects of such organophosphate contamination continues to reverberate.

Carson’s timely work focused primarily on the devastating environmental and human impacts of DDT. But today, a University of New England researcher has led a team characterizing a related pesticide, chlorpyrifos, a widely used contaminant with potentially lasting detrimental effects on the human nervous system.  

Matthew Havrda, Ph.D., associate dean for Research and Scholarship in UNE’s College of Osteopathic Medicine, has led a multidisciplinary research team that has identified new evidence illustrating the neurotoxic effect of chronic exposure to chlorpyrifos.

The study published today in the leading journal Toxicological Sciences builds on decades of research linking  exposure to pesticides, including chlorpyrifos, to age-related neurodegenerative diseases. The team’s findings add mechanistic insights to epidemiological evidence that occupational exposure to the widely used agricultural chemical may contribute to developmental impairments and neurologic disorders, such as Alzheimer’s and Parkinson’s.

The Havrda team’s study — written in collaboration with colleagues from Dartmouth College, Merck Research Laboratories Boston, and the Louisiana State University Agricultural Center — examined the combined effects of aging and chlorpyrifos-contaminated water on the human nervous system and their molecular origin. 

Through animal models, the researchers found that both age and exposure to chlorpyrifos -contaminated water resulted in negative systemic effects to vital organs.

Specifically, Havrda Laboratory graduate researcher Emma Fikse, a doctoral candidate in the Graduate Program in Molecular and Cellular Biology at Dartmouth’s Geisel School of Medicine, observed a loss of key neurons in the brain. This neuronal loss was associated with reductions in the blood protein haptoglobin, suggesting it may be a novel biomarker for detection and risk mitigation in those exposed to organophosphates like chlorpyrifos.

Haptoglobin binds to free hemoglobin — hemoglobin that is present in the blood plasma outside of red blood cells — and inhibits the oxygen-transporting protein from accumulating in the bloodstream. Such accumulation can lead to oxidative stress and cause excessive inflammation, kidney problems, and multisystem organ failure.

The study revealed that chlorpyrifos neurotoxicity was associated with reduced levels of haptoglobin in microglia residing in key brain regions including the hippocampus and striatum. Microglia are critical immune cells that regulate the brain’s response to injury, whose function is compromised in diseases like Alzheimer’s and Parkinson’s. 

“Findings that chlorpyrifos modulates HPT in multiple tissues and experimental models suggest its promise as a practical means of identifying exposure towards preventing chlorpyrifos -related toxicity,” the authors wrote. “Taken together, our findings provide novel mechanistic insights into chlorpyrifos -induced neurodegeneration and lay the groundwork for further investigations into chlorpyrifos toxicity in aging populations, as well as the development of biomarkers for improved risk assessment and monitoring.”  

At UNE, Havrda leads research initiatives for the College of Osteopathic Medicine, Maine’s only medical school and one of the nation’s best medical schools for research, as named by U.S. News & World Report. 

“This work reminds us how little we know about the long-term impacts of widely used agricultural chemicals,” says Havrda, “It is our hope that findings will inform efforts to develop and maintain safe practices that ensure the productivity of our farmers and the healthy aging of their employees, families, and communities.” 

UNE’s medical school — housed in the recently opened Harold and Bibby Alfond Center for the Health Sciences — provides faculty and students with experiential research opportunities that span both qualitative and quantitative methods. 

Student learning is supplemented with access to world-class biomedical research facilities on both of Maine’s coastal campuses, including the Pickus Center for Biomedical Research in Biddeford and the Portland Laboratory for Biotechnology and Health Sciences (PLBHS).

Inaugurated in 2023 on UNE’s Portland Campus for the Health Sciences — the only fully integrated, interprofessional health sciences campus of its kind in New England — the PLBHS fosters collaborative, interdisciplinary research that addresses local and global needs while facilitating opportunities for strategic research partnerships in industry directly contributing to workforce development in one of Maine’s fastest-growing research sectors.