Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo.
Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo.
复制标题
DOI：
10.3390/medsci4030013
复制
发表时间：
2016-08-16
期刊：
影响因子：
--
通讯作者：
Caudle WM
中科院分区：
文献类型：
--
作者：
Patel R;Bradner JM;Stout KA;Caudle WM
我们对暴露在环境毒物中对神经系统疾病的贡献的理解继续发展。其中，帕金森氏病(PD)已被证明与其发病机制有很强的环境因素。然而，仍然需要工作来识别和表征可能改变黑质纹状体多巴胺系统的表达和功能的环境化学物质。特别令人感兴趣的是全氟化合物的神经毒理学效应，如全氟辛烷磺酸(PFOS)，已被证明改变了多巴胺信号转导的各个方面。使用体外实验方法，我们阐述了这些初步发现，以证明全氟辛烷磺酸对SH-SY5Y神经母细胞瘤细胞系和多巴胺能原代培养神经元的神经毒性。使用活体模型，我们没有观察到接触10 mg/kg全氟辛烷磺酸14天的小鼠纹状体内多巴胺能终末的缺失。然而，随后暴露于选择性多巴胺能神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)后，显著降低了多巴胺转运体(DAT)和酪氨酸羟基酶(TH)的表达，并导致先前暴露于全氟辛烷磺酸的动物DAT表达的下降更大。这些发现表明，全氟辛烷磺酸对黑质纹状体多巴胺回路具有神经毒性，这种神经毒性可能使多巴胺终末在额外的毒理学侮辱后受到更广泛的损害。
Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize environmental chemicals that could alter the expression and function of the nigrostriatal dopamine system. Of particular interest is the neurotoxicological effect of perfluorinated compounds, such as perfluorooctane sulfonate (PFOS), which has been demonstrated to alter aspects of dopamine signaling. Using in vitro approaches, we have elaborated these initial findings to demonstrate the neurotoxicity of PFOS to the SH-SY5Y neuroblastoma cell line and dopaminergic primary cultured neurons. Using an in vivo model, we did not observe a deficit to dopaminergic terminals in the striatum of mice exposed to 10 mg/kg PFOS for 14 days. However, subsequent exposure to the selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly reduced the expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH), and resulted in an even greater reduction in DAT expression in animals previously exposed to PFOS. These findings suggest that PFOS is neurotoxic to the nigrostriatal dopamine circuit and this neurotoxicity could prime the dopamine terminal to more extensive damage following additional toxicological insults.