ToxSci Advance Access published online on February 11, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp029
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Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain
Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden
Correspondence to: Henrik Viberg, Department of Environmental Toxicology ,Uppsala University, Norbyvägen 18 A, S-752 36 Uppsala Sweden, Telephone: +46 18 4717695, Fax: +46 18 518843, e-mail: Henrik.Viberg{at}ebc.uu.se
Received December 19, 2008; revision received February 3, 2009; accepted February 4, 2009
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Abstract |
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Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) belong to the family of perfluorinated compounds (PFCs). They are used in industrial and consumer applications, e.g. clothing fabrics, carpets and food packaging. PFOS and PFOA are present in the environment and are found in dust and human milk, which implies that newborns and toddlers can be directly exposed to these agents during brain development. Recently, we reported that PFOS and PFOA can cause neurobehavioral defects and changes in the cholinergic system, in the adult animal, when given directly to neonatal mice, and thereby showing similarities with other investigated persistent organic pollutants (POPs), such as DDT, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). In recent studies, we have also seen that highly brominated PBDEs can affect the levels of proteins that are important for neuronal growth and synaptogenesis in the neonatal mouse brain. The present study shows that a single oral dose of either 21 µmol PFOS or PFOA/kg body weight (11.3 mg or 8.70 mg), given directly to the neonatal mice on postnatal day 10, significantly increased the levels of CaMKII, GAP-43, and synaptophysin in the hippocampus of the neonatal mouse. Both compounds significantly increased the levels of synaptophysin and tau in cerebral cortex and PFOA also increased the levels of tau in hippocampus. Since these proteins are important for normal brain development and altered levels of these proteins during a critical period of the brain growth spurts (BGS) could be one of the mechanisms behind earlier reported behavioral defects.
Key Words: PFCs; Neurotoxicity; CaMKII; GAP-43; Synaptophysin; Tau.