Anti-SYN1 (native protein) polyclonal antibody

Viral vectors are excellent tools for studying gene function in the brain, although a limitation has been the ability to effectively target transgene expression to specific neuronal populations. This generally cannot be overcome by the use of neuron-specific promoters, as most are too large to be used with current viral vectors and expression from these promoters is often relatively weak. We therefore developed a composite expression cassette, comprising 495 by of the weak human SYN1 (synapsin-1) promoter and 800 by of the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE). Studies in hippocampal cultures, organotypic cultures, and in vivo showed that the 3' addition of the WPRE to the SYN1 element greatly increased enhanced green fluorescent protein expression levels with no loss of neuronal specificity. In vivo studies also showed that transgene expression was enhanced with no loss of neuronal specificity in dentate-gyrus neurons for at least 6 weeks following transfection. Therefore, unlike most powerful promoter systems, which mediate expression in neurons and glia, this SYN1-WPRE cassette can target powerful long-term transgene expression to central nervous system neurons when delivered at relatively low titers of adenovirus. Its use should therefore facilitate both gene therapy studies and investigations of neuronal gene function.

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.