The Effect Of PFOS On The BDNF/TrkB/CREB Signualing Pathway In Nerve Cells

Perfluorooctane sulfonate(PFOS) is a perflouorinated compounds(PFCs), which is widely distributed in the environment. Previous studies indicated that PFOS could result in toxicity of liver, heart, hung, and immunity system, etc. Since PFOS can pass through the placental barrier and brain blood barrier, the developmental neurotoxicity of PFOS has been attracted more attention. Pregnant Kunming mices were exposed to PFOS to establish a modle of developmental toxicity of PFOS. HE staining was used to observe the effects of PFOS on hippcampus and cortex of neonatal mices. QPCR was applied to detect the key genes m RNA levels of the BDNF/Trk B/CREB signaling pathway in offspring’s hippocampus. The results showed that PFOS exposure damage the hippocampal tissue, resulting in cavitation bubble appearance in the hippocampus, and decreased the m RNA levels of BDNF, Trk B and CREB as well as synaptic associated proteins Syn1 and Syp. In addition, the SH-SY5 Y cells were treated by PFOS to establish a vitro model of PFOS toxicity. The results indicated that PFOS could inhibit the proliferation of SH-SY5 Y cells, decreased the m RNA levels of BDNF, and decreased the protein levels of BDNF, Trk B and CREB, which were consistent with the results of the vivo study. In conclusion, PFOS could damage the BDNF/Trk B/CREB signalingpathways in nerve cells, which may be a mechanism of neurotoxicity of PFOS.Part1: Effect of prenatal exposure to perfluorooctane sulfonate on BDNF/Trk B/CREB signaling pathway in mice offspring’s hippocampusObjective: The aim is to study the developmental neurotoxicity of PFOS and its mechanisms. Methods: Pregnant Kunming mices were administrated 0.1, 1.0 and 5.0mg/kg /day PFOS by gavage from gestation day(GD) 2 to postnatal day(PND) 21, control group received 0.05% Tween-20. The offspring’s brain tissue were collected and observed by HE staining on the PND21. QPCR was used to detect m RNA level of BDNF, Trk B, CREB, Syn1 and Syp in the offspring’s hippocampus. Result: Vacuole was observed in offspring’s hippocampus tissue on PND21 in 5.0mg/kg/d PFOS group. Compared with control group, the m RNA levels of BDNF, Trk B and CREB were significantly decreased in 5.0mg/kg PFOS group. The m RNA levels of Syn1 and Syp in 1.0 and 5.0 mg/kg/d PFOS group were significantly lower than in the control group. Conclusions: PFOS exposure could decrease the expression of BDNF, Trk B, CREB, Syn1 and Syp, which may play an important role in the developmental neruotoxicity of PFOS.Part2: The effect of perfluorooctane sulfonate on BDNF/Trk B/CREB signaling pathway in SH-SY5 Y cellsObjective: The aim is to investigate the damage effect of perfluorooctane sulfonat(PFOS) and the gene expression changes of BDNF/Trk B/CREB signaling pathwayon SH-SY5 Y cells, and to explore the mechanisms of neurotoxicity of PFOS. Methods: SH-SY5 Y cells were divided into four groups:control group, 10μM PFOS group, 50μM PFOS group, 100μM PFOS group, 150μM PFOS group and 200μM PFOS group. The cells were treated with PFOS 48 h, and then cell activity was determined with MTT assay. The m RNA or protein expression of BDNF were detected by QPCR or ELISA, respectively. Western blot was used to determine protein levels of Trk B, CREB and p-CREB. Result: With the incerase of PFOS comcentration, the survival rate of SH-SY5 Y cells decreased increasingly. The difference between the experimental groups(50μM, 100μM PFOS) and control group was significant(P<0.05). PFOS inhibited the expression of BDNF, Trk B and CREB, but increased the p-CREB. Conclusion: PFOS exposure decreased the cells activity and changed the key gene expression of BDNF/Trk B/CREB signaling pathway. This might be the one of the mechanisms of PFOS neurotoxicology.