PFAS Toxic Effects Induced Neurotoxicity: A Growing Concern in Environmental Health

By SWA

Recent research has brought to light alarming evidence of how per- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals,” may contribute to neurotoxicity by disrupting the normal functioning of genes critical for brain development and cognitive health. In a groundbreaking study conducted by scientists at the University at Buffalo, 11 key genes have been identified as potential markers to detect and monitor the brain's response to PFAS-induced damage.

“Our findings indicate these genes may be markers to detect and monitor PFAS-induced neurotoxicity in the future,” said Dr. G. Ekin Atilla-Gokcumen, the study's lead co-corresponding author and a distinguished professor in the Department of Chemistry at UB's College of Arts and Sciences. Among the six types of PFAS analyzed, perfluorooctanoic acid (PFOA) — a compound previously used in nonstick pans and recently classified as hazardous by the U.S. Environmental Protection Agency (EPA) — emerged as the most disruptive, altering the expression of nearly 600 genes. By comparison, no other PFAS tested altered more than 147 genes.

PFAS and the Nervous System

Neurotoxic PFAS refers to PFAS compounds capable of damaging the nervous system, including the brain, spinal cord, and peripheral nerves. These synthetic chemicals are widely used in consumer and industrial products such as nonstick cookware, firefighting foams, food packaging, and textiles. Their chemical stability and resistance to breakdown make PFAS environmentally persistent and capable of bioaccumulating in living organisms, leading to long-term health concerns.

One of the most troubling effects of PFAS exposure is its impact on the nervous system, particularly during early development. Researchers have uncovered evidence that PFOA and other PFAS compounds can cross the blood-brain barrier — the protective shield that isolates the brain from toxins in the bloodstream. Once inside the brain, PFAS interfere with critical cellular processes, including synaptic growth, neurotransmission, and oxidative stress management.

Gene Expression Alterations: A Closer Look

The University at Buffalo study revealed that PFAS exposure induces widespread changes in gene expression. Of particular concern are genes linked to synaptic plasticity, neurodevelopment, neurotransmission, and inflammation — processes vital for normal brain function. Notably, PFOA reduced the expression of genes critical for synaptic growth and neural function, which are essential for learning, memory, and cognition.

Here are key categories of genes affected by PFAS and their implications:

1. Genes Regulating Oxidative Stress and Detoxification

PFAS induce oxidative stress in neuronal cells by altering the expression of genes responsible for managing reactive oxygen species (ROS):

  • NRF2 (NFE2L2): A master regulator of the antioxidant response. PFOA exposure suppresses NRF2, impairing the brain’s ability to protect itself from oxidative damage.
  • SOD1 and SOD2: Genes encoding enzymes that neutralize ROS. PFAS exposure disrupts their function, contributing to neuronal damage.

2. Genes Linked to Neuroinflammation

Chronic inflammation is a key mechanism of PFAS-induced neurotoxicity:

  • IL-6 (Interleukin-6) and TNF-α (Tumor Necrosis Factor-alpha): Pro-inflammatory cytokines that are upregulated in response to PFAS exposure.
  • NF-κB (Nuclear Factor Kappa B): A transcription factor activated by PFAS, leading to increased inflammation and damage to neural tissues.

3. Neurodevelopment and Synaptic Plasticity Genes

PFAS disrupt neurodevelopmental processes, particularly during prenatal and early life:

  • BDNF (Brain-Derived Neurotrophic Factor): A key protein for synaptic growth and cognitive function. PFAS exposure downregulates BDNF, impairing memory and learning.
  • MAPK1 and ERK1/2: Components of signaling pathways essential for brain development and plasticity, disrupted by PFAS.

4. Endocrine-Related Genes

As endocrine disruptors, PFAS interfere with hormones critical for brain function:

  • THRA and THRB (Thyroid Hormone Receptors): PFAS exposure reduces thyroid hormone signaling, negatively impacting brain development.
  • ESR1 and ESR2 (Estrogen Receptors): Disrupted estrogen signaling contributes to impaired neuroprotection and synaptic function.

5. Neurotransmitter System Genes

PFAS interfere with neurotransmitter systems that regulate mood, behavior, and cognition:

  • SLC6A4: Regulates serotonin reuptake, which is critical for mood and behavior. PFAS disrupt its expression, potentially contributing to anxiety and depression.
  • TH (Tyrosine Hydroxylase): A key enzyme in dopamine synthesis, which is altered by PFAS exposure, potentially impairing reward and motivation pathways.

Implications for Public Health

The cumulative impact of PFAS on these genes poses significant risks for neurological health, especially for vulnerable populations like pregnant women, children, and individuals with high environmental exposure. Developmental neurotoxicity — disruptions in brain development due to prenatal or early-life exposure — is a major concern. This can lead to cognitive deficits, behavioral issues (such as ADHD), and developmental delays.

Furthermore, adults exposed to PFAS over time may face an increased risk of neurodegenerative diseases like Alzheimer’s and Parkinson’s, as PFAS disrupt key genes involved in protein aggregation (e.g., APP, associated with amyloid plaque formation) and neuronal health (e.g., SNCA, linked to Parkinson’s disease).

Addressing PFAS Neurotoxicity

  1. Regulatory Action: Governments worldwide are implementing stricter regulations on PFAS production and use. In the U.S., the EPA has declared PFOA and PFOS hazardous substances and is pushing for limits on PFAS levels in drinking water.
  2. Research and Monitoring: The identification of specific gene markers, as highlighted by the University at Buffalo study, offers new opportunities for early detection and monitoring of PFAS-induced neurotoxicity.
  3. Reducing Exposure: Individuals can limit their exposure by avoiding products containing PFAS, using water filters that remove these chemicals, and supporting environmentally friendly alternatives in manufacturing.

Conclusion

The study by the University at Buffalo underscores the urgent need to address the neurotoxic effects of PFAS exposure. By altering the expression of hundreds of genes — particularly those involved in synaptic function and brain development — PFAS pose a serious threat to public health. Continued research is critical to uncover the full extent of PFAS-induced neurotoxicity and to develop effective strategies for prevention and treatment. For now, reducing exposure and strengthening regulatory measures remain essential steps in protecting human health from the dangers of these persistent chemicals.

Read: Cooking Utensils That Are Not PFAS-Free

Reference:
Forever Chemicals in the Brain? New Study Exposes Silent Invasion

Underestimated burden of per- and polyfluoroalkyl substances in global surface waters and groundwaters

Sum of concentration of 20 PFAS subject to EU guidance in surface water, groundwater and drinking water samples. 
 
Australia: Drinking PFAS’: water providers call for broad ban on ‘forever chemicals’ amid proliferation fears https://www.theguardian.com/environment/2025/jan/22/pfas-water-providers-call-for-ban-forever-chemicals

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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