| Perfluorooctane sulfonate (PFOS) is prominent members of the family of perfluorinated alkyls (PFAs), which have been widely used in manufactures and human life. Due to the environmental persistence and world-wide distribution through food webs, PFOS has been detected in wildlife and human serum (occupational and non-occupational people). In 2009, PFOS was suggested to be included in the group of persistent organic pollutants.Hippocampus, which is important for learning and memory, is the target organ for PFOS. Calcium signaling plays an omportant role in mediating the structure and function of the central nervous system, special in learning and study. Many pollutants in the environment had effect on the central nervous system by mediating calcium signaling. It is important parts to investigate the neurotoxic effect of PFOS in evaluate the health risk of PFOS and related compounds.The following parts are included in the study and results:(1) Adult male Sprague-Dawley rats were administered with PFOS at dosages of 1.7,5.0 and 15.0 mg/L in drinking water for 91 consecutive days. Western blot was employed to determine the expression of CaMKIIa and pCREB in the isolated cortex and hippocampus. The expression of c-fos and c-jun was detected by real-time reverse transcription polymerase chain reaction. The results showed that PFOS can be detected in cortex and the expression levels of CaMKⅡαand pCREB exhibited a dose-dependent increase in cortex and hippocampus after treatment with PFOS, compared with control. The transcription factors c-fos and c-jun were also up-regulated in cortex and hippocampus. The results indicated that PFOS might induce neurotoxic effect on adult male Sprague-Dawley rats by mediating the molecules in calcium signaling.(2) Effect of gestational and lactational exposure to PFOS on central nervous system (CNS) in Wistar rats was investigated by the cross-foster model built with PFOS at 0 or 3.2 mg/kg food. Real-time reverse transcription polymerase chain reaction was employed to evaluate the gene expression of calcium-dependent signaling molecules in rats' hippocampus which are critical to the function of CNS. The expression of calcium-related signaling molecules, such as N-methyl-d-aspartate receptor subtype-2B (NR2B), calmodulin (CaM), CaMKIIa and CREB were increased in the PFOS exposure group at postnatal day 1 (PND 1). The decreased NR2B in the prenatal PFOS exposure group, the decreased CaM in the pre-/postnatal PFOS exposure group, the increased CaMKIIa in the wholelife PFOS exposure group and the increased CREB in the prenatal/wholelife PFOS exposure group was observed at PND 7. At PND 35, rats exhibited the decreased NR2B in the pre-/postnatal and the whole life PFOS exposure group, and the decreased CaM in the postnatal PFOS group. The results indicate that perinatal exposure to PFOS during the critical period of development of the brain may have neurotoxic effect on CNS by mediating the molecules of calcium signaling pathway.(3) In the present study, the concentration of the compounds in primary cultures of rat hippocampal neurons was analyzed by HPLC/MS/MS. Flow cytometry was used to examine the altered calcium in neurons labeled with fluo-3/AM and to disclose the exact mechanism in PFOS-or perfluorooctanoate (PFOA)-induced calcium increase in cultured neurons. The results showed that PFOS or PFOA could accumulate in cultured neurons, and elevate calcium by intracellular way. Furthermore, IP3Rs and RyRs were found to take part in PFOS or PFOA inducing calcium release from calcium store. IP3Rs seem to serve a predominant role in triggering calcium increase in PFOS-induced calcium release. Calcium release from intracellular store may partially account for the perturbation of calcium homeostasis caused by PFOS or PFOA.In summary, PFOS induced calcium ion increased by calcium influx through NR2B and calcium release from calcium store in cell through IP3Rs and RyRs, followed by the abnormal expression of CaM, CaMKII, CREB, c-fos and c-jun in calcium signaling the central nervous systemhas, leading to the dysfunction of the central nervous system.
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