title: Neurotoxicity of perfluorooctane sulfonate to hippocampal cells in adult mice.
abstract: Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant and found in the environment and in biota. The neurotoxicity of PFOS has received much concern among its various toxic effects when given during developing period of brain. However, little is known about the neurotoxic effects and potential mechanisms of PFOS in the mature brain. Our study demonstrated the neurotoxicity and the potential mechanisms of PFOS in the hippocampus of adult mice for the first time. The impairments of spatial learning and memory were observed by water maze studies after exposure to PFOS for three months. Significant apoptosis was found in hippocampal cells after PFOS exposure, accompanied with a increase of glutamate in the hippocampus and decreases of dopamine (DA) and 3,4-dihydrophenylacetic acid (DOPAC) in Caudate Putamen in the 10.75 mg/kg PFOS group. By two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis, seven related proteins in the hippocampus that responded to PFOS exposure were identified, among which, Mib1 protein (an E3 ubiquitin-protein ligase), Herc5 (hect domain and RLD 5 isoform 2) and Tyro3 (TYRO3 protein tyrosine kinase 3) were found down-regulated, while Sdha (Succinate dehydrogenase flavoprotein subunit), Gzma (Isoform HF1 of Granzyme A precursor), Plau (Urokinase-type plasminogen activator precursor) and Lig4 (DNA ligase 4) were found up-regulated in the 10.75 mg/kg PFOS-treated group compare with control group. Furthermore, we also found that (i) increased expression of caspase-3 protein and decreased expression of Bcl-2, Bcl-XL and survivin proteins, (ii) the increased glutamate release in the hippocampus. All these might contribute to the dysfunction of hippocampus which finally account for the impairments of spatial learning and memory in adult mice.
authors: Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
authors: Yan
authors: Y
authors: Long
authors: Yubang
authors: Y
authors: Wang
authors: Guixiang
authors: G
authors: Ji
authors: Lifeng
authors: L
authors: Yan
authors: Fan
authors: F
authors: Hu
authors: Aihua
authors: A
authors: Gu
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005466:Fluorocarbons / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D015102:3,4-Dihydroxyphenylacetic Acid; D018698:Glutamic Acid; C076994:perfluorooctane sulfonic acid; D053148:Caspase 3; D004298:Dopamine
references: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3196-200
references: 8159723
references: Chemosphere. 2013 Feb;90(5):1597-602
references: 22990021
references: J Pharmacol Exp Ther. 2006 Dec;319(3):1172-81
references: 16973885
references: Environ Sci Technol. 2008 Jul 1;42(13):4989-95
references: 18678038
references: Environ Sci Technol. 2007 Jun 1;41(11):3891-7
references: 17612165
references: Proc Natl Acad Sci U S A. 2004 Oct 5;101(40):14515-20
references: 15452348
references: Curr Biol. 1996 Nov 1;6(11):1509-18
references: 8939606
references: Environ Sci Technol. 2001 Apr 1;35(7):154A-160A
references: 11348100
references: Neurotoxicology. 2008 Jan;29(1):160-9
references: 18063051
references: Neurotoxicology. 2012 Jun;33(3):314-20
references: 22326494
references: Neurobiol Dis. 2012 Apr;46(1):215-24
references: 22293605
references: Mol Cell Proteomics. 2004 May;3(5):501-9
references: 14963112
references: J Neurosci. 2008 Dec 31;28(53):14443-9
references: 19118178
references: Environ Health Perspect. 2003 Sep;111(12):1485-9
references: 12948888
references: Nat Immunol. 2004 Sep;5(9):883-90
references: 15334084
references: Toxicol Sci. 2009 Apr;108(2):412-8
references: 19211617
references: Mol Cell Proteomics. 2003 Jan;2(1):19-28
references: 12601079
references: Environ Sci Technol. 2001 Apr 15;35(8):1593-8
references: 11329707
references: Br J Pharmacol. 2003 Mar;138(6):1021-5
references: 12684256
references: Genes Dev. 2009 Jan 15;23(2):171-80
references: 19171781
references: Brain Res Brain Res Rev. 2001 Aug;36(1):60-90
references: 11516773
references: J Histochem Cytochem. 2003 Jul;51(7):873-85
references: 12810838
references: Alcohol Clin Exp Res. 2001 Feb;25(2):185-91
references: 11236831
references: Toxicology. 2007 Dec 5;242(1-3):123-9
references: 17950980
references: Neurotoxicology. 2011 Jan;32(1):130-9
references: 20937303
references: Environ Health Perspect. 2012 May;120(5):752-7
references: 22271837
references: Reprod Toxicol. 2009 Jun;27(3-4):387-399
references: 19429409
references: Hum Mol Genet. 2005 Jan 1;14(1):125-33
references: 15548549
references: Biol Cell. 1996;88(1-2):45-54
references: 9175267
references: J Pharmacol Exp Ther. 2006 Aug;318(2):589-95
references: 16687476
references: Environ Sci Technol. 2006 Apr 1;40(7):2128-34
references: 16646443