A study in rats found that exposure to perfluorooctane sulfonic acid (PFOS) altered gene expression in the nucleus accumbens, hippocampus, and prefrontal cortex regions of the offspring’s brains. This may have resulted in decreased cognitive ability and more impulsive decision-making. This paper was published in the journal Ecotaxology and Environmental Safety.
Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals widely used in industrial processes and consumer products because of their resistance to heat, water, and oil. One of these chemicals is perfluorooctane sulfonic acid (PFOS). It is a traditional substance that has been used for decades in products and certain manufacturing processes such as firefighting foam and antifouling coatings. They are sometimes referred to as “forever chemicals” because they break down very slowly and can persist in the environment for very long periods of time.
Although the use of PFOS was largely discontinued in the early 21st century, PFOS continues to be widely present in both the environment and the human body. PFOS resists metabolic degradation and accumulates in the body for long periods of time. Although overall levels of PFAS in the environment have decreased in recent years, PFOS remains the most frequently detected PFAS in human blood. Humans are primarily exposed to PFOS through contaminated water, food, dust, and consumer products.
Studies have shown that exposure to PFOS has negative effects on the human body, including changes in cholesterol levels, liver-related measures, immune responses, and pregnancy-related outcomes. Because of these concerns, the production and use of PFOS has been severely restricted or phased out in many parts of the world.
Study author Shiwen Li and colleagues wanted to investigate how prenatal PFOS exposure affects gene expression in three major regions of the brain: the nucleus accumbens, hippocampus, and prefrontal cortex. These three regions were chosen because the nucleus accumbens is central to motivation and behavior, the hippocampus is important for learning and memory, and the prefrontal cortex is essential for executive function and working memory. The authors also wanted to know whether changes in gene expression in these three regions were associated with behavioral changes in rats exposed to PFOS.
This study was conducted on Long Evans rats. Pregnant female rats entered the study from day 12 of embryonic development and gave birth to offspring naturally. Rats had free access to food and water.
Pregnant female rats were divided into two groups of six rats each. One group was exposed to PFOS through drinking water that contained 15 mg of PFOS per liter and a small amount of Tween 20 (a chemical used as an admixture). The control group drank water containing only Tween 20 and no PFOS. Exposure began on the 12th day of rat gestation and continued until weaning, which occurred 21 days after rat pups were born.
Once the offspring reached adulthood, they completed a series of behavioral tests, including an extradimensional set-shifting task (switching from directional to visual cues) and a delay discounting task. After these tests, the study authors performed RNA sequencing on adult male rat brain tissue and analyzed gene expression in three focal brain regions.
The results showed that 62 genes were differentially expressed in the nucleus accumbens tissues of rats exposed to PFOS. The number of differentially expressed genes in the hippocampus was 34, and the number of differentially expressed genes in the prefrontal cortex was 59. Differential expression of genes means that those genes are more or less active in the PFOS-exposed group compared to the control group. These changes can change how affected cells function, react, and develop.
Specifically, the researchers observed changes in genes involved in extracellular matrix interactions within the nucleus accumbens, the brain’s structural support system. In the prefrontal cortex, PFOS exposure disrupted genes responsible for glutathione metabolism, a key biological pathway the brain uses to remove harmful oxidative stress and toxins.
Statistical analysis showed that differential expression of some of these genes may mediate the association between PFOS exposure and behavioral test results. Although the rats did not show significant impairments in cognitive flexibility, the results showed that certain genetic changes were strongly associated with more impulsive decision-making. For example, rats exposed to PFOS had a lower preference for large, delayed rewards compared to small, immediate rewards, and gave up more often as waiting time increased.
“PFOS exposure during development can alter gene expression in the nucleus accumbens and prefrontal cortex, which was associated with decreased cognitive flexibility and impulsive decision-making,” the study authors conclude in their abstract.
This study contributes to the scientific understanding of the effects of PFOS on nervous system development. However, it is important to note that this study was conducted on rats, not humans. Although rats and humans have many physiological similarities, they are still different species, and results in humans may be different. Furthermore, because the study used a single dose of the chemical, it remains unclear how the severity of the outcome changes with higher or lower environmental doses.
The paper, “Perfluorooctane sulfonic acid (PFOS) exposure during development alters gene expression in the nucleus accumbens and prefrontal cortex and impairs cognition in rats: transcriptomic and mediational analysis,” was authored by Shiwen Li, Hongxu Wang, Ana C. Maretti-Mira, Tomas KD Manea, Shaun Y. Kim, Lida Chatzi, Jesse A. Goodrich, and Tanya L.. Alderete, Nathan Young, Ruth I. Wood, and Max T. Aoun.
