A groundbreaking study from the University at Buffalo has identified 11 genes that are consistently affected by PFAS exposure, providing new insights into the neurotoxic effects of these “forever chemicals.”
A recent study by researchers at the University at Buffalo (UB) has unveiled significant molecular clues about the neurotoxic effects of per- and polyfluorinated alkyl substances (PFAS), commonly known as “forever chemicals.”
PFAS have garnered significant concern due to their persistence in water, soil and even the human brain. These chemicals’ ability to cross the blood-brain barrier and accumulate in brain tissue necessitates further research into their neurotoxic mechanisms.
The UB study has identified 11 genes that may be pivotal in understanding how these pervasive chemicals impact the brain.
“Our findings indicate these genes may be markers to detect and monitor PFAS-induced neurotoxicity in the future,” lead co-corresponding author G. Ekin Atilla-Gokcumen, a Dr. Marjorie E. Winkler Distinguished Professor in UB’s Department of Chemistry, said in a news release.
The study, published in the journal ACS Chemical Neuroscience, revealed hundreds more genes whose expressions varied based on the PFAS compounds tested. This highlights that the molecular structure of each PFAS plays a critical role in how genes are expressed.
“PFAS, despite sharing certain chemical characteristics, come in different shapes and sizes, leading to variability in their biological effects. Thus, knowledge on how our own biology reacts to the different types of PFAS is of major biomedical relevance,” added co-corresponding author Diana Aga, a SUNY Distinguished Professor, Henry M. Woodburn Chair in UB’s Department of Chemistry and director of the UB RENEW Institute.
PFAS exposure in daily life, from drinking water to food packaging, typically goes unnoticed because they are not immediately toxic. Consequently, researchers need to explore upstream cellular processes beyond merely cell survival or death.
By focusing on the effect of PFAS on the gene expression of neuronal-like cells and lipid changes, the UB team identified significant alterations. For instance, perfluorooctanoic acid (PFOA), once widely used in nonstick cookware and now deemed hazardous by the EPA, had the most profound impact, altering the expression of nearly 600 genes.
The six PFAS compounds tested affected pathways critical for neuronal function and development, such as hypoxia signaling, oxidative stress, protein synthesis and amino acid metabolism. Among the genes that expressed uniformly in response to all six compounds, mesencephalic astrocyte derived neurotrophic factor (linked to neuronal cell survival) decreased and thioredoxin interacting protein (associated with neuronal cell death) increased.
“Each of these 11 genes exhibited consistent regulation across all PFAS that we tested. This uniform response suggests that they may serve as promising markers for assessing PFAS exposure, but further research is needed to know how these genes respond to other types of PFA,” Atilla-Gokcumen added.
As PFAS are integral to numerous industrial applications, such as firefighting and semiconductor manufacturing, finding safer alternatives is challenging. Understanding the distinct molecular impacts of various PFAS can help phase out the most harmful compounds while seeking safer substitutes.
“If we understand why some PFAS are more harmful than others, we can prioritize phasing out the worst offenders while seeking safer substitutes,” Atilla-Gokcumen added.
This study is a significant step toward making informed decisions about future PFAS use and substitution strategies.
The groundbreaking research emphasizes the complexity and diversity of PFAS and their unique biological effects, paving the way for future studies on safer alternatives.