title: 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 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.
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.|Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tsuyama
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Sanoh
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan. yaichiro@hiroshima-u.ac.jp.
authors.forename: Yaichiro
authors.initials: Y
authors.lastname: Kotake
mesh_terms: D000284:Administration, Oral; D017738:Alkanesulfonic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D017738:Alkanesulfonic Acids; D018690:Excitatory Amino Acid Agonists; D005466:Fluorocarbons; D018091:Receptors, AMPA; C076994:perfluorooctane sulfonic acid; C104722:glutamate receptor ionotropic, AMPA 2; D007608:Kainic Acid
keywords: Brain–plasma ratio; GluR2; Neurotoxicity; PFOS