pfas exposure alters brain genes neurotoxicity risks

PFAS Exposure Alters Brain Genes, Reveals Neurotoxicity Risks-University at Buffalo Study

Introduction to PFAS and their Risks

Per-and polyfluorinated alkyl substances (PFAS), commonly referred to as 'forever chemicals,' are recognized for their resilience in water, soil and human brain tissue. This capacity to bypass the blood-brain barrier and deposit in brain cells heightens their profile, necessitating deeper exploration into their neurotoxic effects.

Study Overview: Identifying Key Genes Affected by PFAS

A recent study conducted by researchers at the University at Buffalo has pinpointed 11 genes that could elucidate the brain's response to these ubiquitous chemicals found in everyday products. The findings are detailed in ACS Chemical Neuroscience.

Gene Expression Changes Due to PFAS Exposure

These genes, many of which play crucial roles in maintaining neuronal health, were consistently impacted by PFAS exposure, either upregulated or downregulated, irrespective of the specific PFAS compounds tested.

• Reduced Expression: One gene essential for neuronal cell survival was downregulated.
• Increased Expression: A gene associated with neuronal cell death was upregulated.

Insights from the Study's Lead Authors

According to G. Ekin Atilla-Gokcumen, Ph.D., lead co-corresponding author and Dr. Marjorie E. Winkler Distinguished Professor in the Department of Chemistry at UB, "Our findings suggest that these genes could serve as markers for detecting and monitoring PFAS-induced neurotoxicity in the future."

Additional Findings on Gene Expression Variability

However, the study revealed that hundreds of additional genes exhibited changes in expression, with variations depending on the compound tested. Furthermore, no correlation was found between the levels of PFAS accumulation in a cell and the degree of differential expression.

Impact of Molecular Structures on Gene Expression

Collectively, these findings indicate that the unique molecular structure of each PFAS type influence changes in gene expression.

"Although PFAS share some common chemical traits, their varying shapes and sizes result in differences in their biological effects. Understanding how our biology responds to the diverse types of PFAS is therefore of significant biomedical importance," states Diana Aga, Ph.D., the study's co-corresponding author, SUNY Distinguished Professor, Henry M. Woodburn Chair in the Department of Chemistry, and director of the UB RENEW Institute."

Investigating the Effects of PFAS on Cellular Processes

The Importance of Studying Lipids and Gene Expression

Atilla-Gokcumen further emphasizes, "Depending on the chain length or headgroup, PFAS can have significantly different effects on cells. We should not treat them as a single class of compounds, but rather as distinct compounds that warrant individual investigation."

Also contributing to the study are Omer Gokcumen, Ph.D., a professor in the Department of Biological Sciences.

Changes in Gene Expression Patterns in Neuronal Cells

PFAS do not exhibit immediate toxicity. We encounter them regularly, such as in drinking water and food packaging, often without awareness.

Atilla-Gokcumen emphasizes that researchers must identify earlier points of assessment in the cellular process, beyond simply determining whether a cell survives or dies.

Detailed Impact of PFAS on Lipids and Genes

Observations from PFAS Exposure in Neuronal-like Cells

The research team chose to investigate the impact of PFAS on the gene expression of neuronal-like cells and on lipids, molecules crucial for the cell membrane and other key functions. After 24-hour exposure to various PFAS, they observed moderate yet distinct alternations in lipid composition, along with differential expression in over 700 genes.

PFOA: The Most Impactful Compound

Among the six PFAS compounds tested, perfluorooctanoic acid (PFOA), which was previously used in nonstick cookware and recently classified as hazardous by the EPA, had the most profound impact. Despite minimal uptake, PFOA altered nearly 600 genes, far surpassing any other compound, which affected no more than 147 genes. Notably, PFOA reduced the expression of genes related to synaptic growth and neural function.

Broader Impact on Biological Pathways

Collectively, the six compounds led to alteration in biological pathways related to hypoxia signaling, oxidative stress, protein synthesis, and amino acid metabolism—key processes for neuronal function and development.

Consistent Gene Regulation Across PFAS Compounds

Uniform Gene Expression Patterns

Eleven gene consistently exhibited similar expression patterns—either upregulated or downregulated—across all six compounds. One of the genes consistently downregulated was mesencephalic astrocyte-derived neurotrophic factor, which is critical for neuronal cell survival and has been shown to alleviate symptoms of neurodegenerative diseases in rat models. Conversely, thioredoxin-interacting protein, consistently upregulated, has been associated with neuronal cell death.

"All 11 genes displayed consistent regulation across the PFAS compounds tested. This uniformity in response points to their potential as reliable markers for PFAS exposure assessment, though further research is required to explore how these genes react to different types of PFAS," says Atilla-Gokcumen.

The Challenge of Identifying Safer Alternatives

The Need for Effective Alternatives

Despite the significant harm posed by PFAS, effective alternatives have not yet been identified.

Long-Term Need for PFAS in Critical Applications

While alternatives may be found for uses such as food packaging, their role in critical sectors like firefighting and semiconductor manufacturing may remain indispensable in the foreseeable future.

Evaluating the Harmful PFAS Compounds

As Atilla-Gokcumen points out, studies like are essential. The diverse gene reactions to different compounds, combined with the absence of a direct link between PFAS uptake and gene expression changes, highlights the distinct nature of each compound.

Prioritizing Harmful PFAS and Exploring Safer Substitutes

"By identifying the most harmful PFAS compounds, we can focus on eliminating the worst offenders and pursuing safer altrnatives, short-chain PFAS, which are less persistent in the environment and accumulate less in organisms, are being considered as potential substitutes," Atilla-Gokcumen explains.

"While short-chain PFAS exhibit lower environmental persistence, their effectiveness in certain applications may be compromised, and concerns about potential unforeseen health risks remain. Additional studies are essential to confirm the safety and efficacy of these substitutes for specific uses. This research represent a crucial advancement toward that goal."

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Stay Informed About the Latest on PFAS and Environmental Health!

Understanding the impact of PFAS on human health and the environment is more crucial than ever. With new research revealing the potential neurotoxicity and other harmful effects of these chemicals, staying up-to-date on the latest findings is essential.

For more insights into PFAS research and environmental health issues, explore our other blogs:

• Human Health Issues Blog: Dive Deeper into the complex relationship between chemicals and health in our Human Health Issues Blog.
• FSNews365: Stay informed about emerging scientific breakthroughs and their real-world implications on health and the environment. Visit FSNews365 for more articles.
• Earth Day Harsh Reality: Learn about the environmental impact of chemicals like PFAS and discover solutions to create a sustainable future, Explore Earth Day Harsh Reality.

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