Inflammation-like glial response in rat brain induced by prenatal PFOS exposure

Numerous studies have indicated the neurotoxicity of perfluorooctane sulfonate (PFOS), a persistent and bioaccumulative compound, particularly during developmental stages of higher organisms. To explore the pro-inflammatory effect in the developmental neurotoxicity, effects of prenatal exposure to PFOS on glial activation in hippocampus and cortex were examined in offspring rats. Dams received 0.1, 0.6 and 2.0 mg/kg bw PFOS by gavage from gestational day 2 (GD2) to GD21. Astrocyte activation markers, glial fibrillary acidic protein (GFAP) and 5100 calcium binding protein B (s-100 beta) in hippocampus and cortex were both upregulated on postnatal day 0 (PNDO) or PND21. In addition, the astrocyte activation was accompanied with the elevation of pro-inflammatory cytokines interleukin (IL-1 beta) and tumor necrosis factor (TNF)-alpha. The mRNA levels of pro-inflammatory transcription factors, including activation protein-1 (AP-1), nuclear factor-kappa B (NF-kappa B), and cAMP response element-binding protein (CREB) were also increased, at least in the 2.0 mg/kg group. In addition to the inflammatory response, two synaptic proteins, synapsin 1 (Syn1) and synaptophysin (Syp) were reduced in cortex on PNDO and PND21. In hippocampus, the Syn1 were also reduced, while the Syp were increased in cortex on either PNDO or PND21. Obtained results indicated chronic glial activation with coexisting inflammatory and synapse injury features as a new mechanism of PFOS developmental neurotoxicity, and enhanced expression of AP-1, NF-kappa B and CREB may contributed to the adverse effect. (C) 2010 Elsevier Inc. All rights reserved.