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 Ca2+ 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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Acknowledgments
This work was supported by JSPS KAKENHI (B) Grant Numbers 23310047 (to Y. K.) and 15H02826 (to Y. K.) and Grant-in-Aid for JSPS Fellows Grant Number 14J06534 (to K. I.).
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Ishida, K., Tsuyama, Y., Sanoh, S. et al. Perfluorooctane sulfonate induces neuronal vulnerability by decreasing GluR2 expression. Arch Toxicol 91, 885–895 (2017). https://doi.org/10.1007/s00204-016-1731-x
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DOI: https://doi.org/10.1007/s00204-016-1731-x