Healthcare (Commonwealth Union) – Per- and polyfluorinated alkyl substances (PFAS) are often referred to as “forever chemicals” due to their persistence in water, soil, and even the human brain.
Their ability to cross the blood-brain barrier and accumulate in brain tissue raises significant concerns, though the precise mechanisms behind their neurotoxicity still require further investigation.
In a recent study, researchers from the University at Buffalo discovered 11 genes that may be crucial in understanding the brain’s reaction to these widespread chemicals, which are commonly found in everyday products.
These genes, many of which play essential roles in neuronal health, were consistently affected by PFAS exposure, showing either increased or decreased expression, regardless of the type of PFAS. For instance, all compounds led to reduced expression of a gene critical for neuronal cell survival, while another gene linked to neuronal cell death was expressed more.
The lead co-corresponding author G. Ekin Atilla-Gokcumen, PhD, Dr. Marjorie E. Winkler Distinguished Professor in the Department of Chemistry at UB College of Arts and Sciences indicated that their results suggest that these genes could serve as markers for detecting and tracking PFAS-induced neurotoxicity in the future.
However, the study, published in the December 18 issue of ACS Chemical Neuroscience, identified hundreds of additional genes whose expression varied in different directions depending on the specific compound tested. Furthermore, there was no clear link between the level of PFAS accumulation in a cell and the extent to which it altered gene expression.
This suggests that the unique molecular structures of each type of PFAS are responsible for the observed changes in gene expression.
Co-corresponding author Diana Aga, PhD, SUNY Distinguished Professor and Henry M. Woodburn Chair in the Department of Chemistry, and director of the UB RENEW Institute pointed out that although PFAS share certain chemical traits, they come in various shapes and sizes, which leads to differences in their biological impacts. Therefore, understanding how our biology responds to these different PFAS types is crucial for biomedical research.
Atilla-Gokcumen stated that depending on their chain length or headgroup, PFAS can have significantly different effects on cells.
She further indicated that we shouldn’t treat them as a single, unified class of compounds, but as individual substances that require separate investigation.
Researchers of the study indicated that PFAS are not acutely toxic, and we are exposed to them almost daily, through sources such as drinking water and food packaging, often without realizing it.
“Therefore, researchers need to find points of assessment further upstream in the cellular process than just whether a cell lives or dies,” added Atilla-Gokcumen.
cells and how they affect lipids, which are vital components of cell membranes and have other key roles. After 24 hours of exposure to various PFAS, the study observed modest yet distinct changes in lipid composition and alterations in the expression of over 700 genes.
Among the six PFAS compounds tested, perfluorooctanoic acid (PFOA)—once widely used in nonstick cookware and recently classified as hazardous by the EPA—had the most significant impact. Despite its limited absorption, PFOA altered the expression of nearly 600 genes, far more than any other compound, which affected fewer than 150 genes. Specifically, PFOA reduced the expression of genes related to synaptic growth and neural function.
Overall, the six PFAS compounds caused changes in biological pathways related to hypoxia signaling, oxidative stress, protein synthesis, and amino acid metabolism—processes that are essential for neuronal function and development.
Eleven genes were consistently affected in the same way—either upregulated or downregulated—by all six compounds. One such gene, mesencephalic astrocyte-derived neurotrophic factor, which is critical for neuronal cell survival and has been shown to reverse neurodegenerative disease symptoms in rats, was consistently downregulated. On the other hand, the gene thioredoxin interacting protein, linked to neuronal cell death, was consistently upregulated.
