Perfluorooctane Sulfonate Induces Neuronal Vulnerability by Decreasing GluR2 Expression
Abstract
Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant. Although studies have described PFOS-induced neurotoxicity in animal brains and neuronal cells, the molecular mechanisms of PFOS-induced neurotoxicity based on the distribution properties, especially during developmental periods, have not been clarified. To clarify the mechanisms of PFOS-induced neuronal vulnerability during developmental periods, we examined changes in glutamate receptor 2 (GluR2) expression and related neurotoxicity in PFOS-treated primary cortical neurons and neonatal rat brains. Exposure of cortical neurons to 1 μM PFOS for 9 days resulted in decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR2 expression, which subsequently enhanced vulnerability to glutamate by increasing intracellular Ca 2+ concentrations. The brain-plasma ratio of PFOS in pups was approximately five times higher than that in dams, although there were no differences in liver-plasma ratio between dams and pups. GluR2 expression in pup cerebral cortex decreased after exposure to 2.0 mg/kg PFOS, and kainic acid induced histopathological abnormalities in PFOS-exposed pups. Our findings suggest that decreased neuronal GluR2 expression is involved in PFOS-induced neurotoxicity, especially during the fetal and neonatal periods.
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More PFAS penetrates to the brain tissue of experimental animals after developmental exposure, in comparison to adult exposures.
“More PFAS penetrates to the brain tissue of experimental animals after developmental exposure, in comparison to adult exposures (Chang et al., 2009; Borg et al., 2010; Ishida et al., 2017).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Ishida et al., 2017
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“More PFAS penetrates to the brain tissue of experimental animals after developmental exposure, in comparison to adult exposures (Chang et al., 2009; Borg et al., 2010; Ishida et al., 2017).”
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- Authors
- Ishida, K., Tsuyama, Y., Sanoh, S., Ohta, S., & Kotake, Y.
- Affiliations
- Hiroshima University (JP)
- Corresponding author
- Kotake, Yaichiro
- Venue
- Archives of Toxicology
- Published
- 2016-05-07
- Volume
- 91
- Issue
- 2
- Pages
- 885-895
- ISSN
- 0340-5761 (ISSN-L)
- 1432-0738
- OpenAlex
- W2392323382
- Cited by
- 27
- References
- 39
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 4
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23310047, 15H02826, 14J06534)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- PFOS, GluR2, AMPA receptors, glutamate excitotoxicity, intracellular calcium, brain-to-plasma ratio, kainic acid, persistent pollutants, cortical neurons, neonatal rat brain
- MeSH terms
- Administration, Oral, Animals, Animals, Newborn, Cell Survival, Cells, Cultured, Cerebral Cortex, Dose-Response Relationship, Drug, Female, Fluorocarbons, Kainic Acid, Neurons, Pregnancy, Tissue Distribution, Rats, Wistar, Alkanesulfonic Acids, Receptors, AMPA, Excitatory Amino Acid Agonists
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