Department of Biology, Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5.
Toxicol Sci. 2011 Apr;120(2):392-402. doi: 10.1093/toxsci/kfq395. Epub 2011 Jan 6.
There is growing interest in assessing the neurotoxic and endocrine disrupting potential of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, prenatal and postnatal development and behavior. PFC exposure altered hormone levels and the expression of hormone-responsive genes in mammalian and aquatic species. This study is the first to assess the effects of PFCs on messenger RNA (mRNA) expression in primary cultures of neuronal cells in two avian species: the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following thyroid hormone (TH)-responsive genes were examined using real-time reverse transcription-PCR: type II iodothyronine 5'-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif-binding factor (Oct-1), and myelin basic protein. Several PFCs altered the mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. Short-chained PFCs (less than eight carbons) altered the expression of TH-responsive genes (D2, D3, TTR, and RC3) in chicken embryonic neuronal cells to a greater extent than long-chained PFCs (more than or equal to eight carbons). Variable transcriptional changes were observed in herring gull embryonic neuronal cells exposed to short-chained PFCs; mRNA levels of Oct-1 and RC3 were upregulated. This is the first study to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and may provide insight into the possible mechanisms of action of PFCs in the avian brain.
人们对评估全氟烷基化合物 (PFCs) 的神经毒性和内分泌干扰潜力越来越感兴趣。有几项研究报告了与神经元发育、神经细胞分化、产前和产后发育以及行为相关的体外和体内效应。PFC 暴露会改变哺乳动物和水生物种的激素水平和激素反应基因的表达。这项研究首次评估了 PFCs 对两种鸟类原代神经元细胞培养物中信使 RNA (mRNA) 表达的影响：家鸡 (Gallus domesticus) 和银鸥 (Larus argentatus)。使用实时逆转录-PCR 检查了以下甲状腺激素 (TH) 反应基因：II 型碘甲状腺原氨酸 5'-脱碘酶 (D2)、D3、转甲状腺素蛋白 (TTR)、神经颗粒蛋白 (RC3)、八聚体基序结合因子 (Oct-1) 和髓鞘碱性蛋白。几种 PFCs 改变了禽类神经元细胞中与 TH 途径相关的基因的 mRNA 表达水平。短链 PFCs(少于 8 个碳原子)比长链 PFCs(等于或多于 8 个碳原子)更能改变鸡胚胎神经元细胞中 TH 反应基因 (D2、D3、TTR 和 RC3) 的表达。暴露于短链 PFCs 的银鸥胚胎神经元细胞中观察到可变的转录变化；Oct-1 和 RC3 的 mRNA 水平上调。这是第一项报道 PFC 暴露改变禽类神经元细胞原代培养物中 mRNA 表达的研究，可能为 PFCs 在禽类大脑中的可能作用机制提供了一些见解。
