Gene expression changes in developing zebrafish as potential markers for rapid developmental neurotoxicity screening
Gene expression changes in developing zebrafish as potential markers for rapid developmental neurotoxicity screening
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DOI：
10.1016/j.ntt.2009.04.065
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发表时间：
2010-01-01
影响因子：
2.9
通讯作者：
Ramabhadran, Ram
中科院分区：
文献类型：
--
作者：
Fan, Chun-Yang;Cowden, John;Ramabhadran, Ram
对于许多化学品而言，指导发育神经毒性风险评估所必需的危险信息有限。由于使用啮齿动物进行发育神经毒性测试既费力又昂贵，因此正在对斑马鱼等替代物种进行调整，以进行快速毒性筛选。以快速通量模式评估化学品的发育神经毒性潜力将有助于识别和表征可以准确和快速测量的转录生物标志物。为此，使用定量真实的时间PCR（qRT-PCR）在受精后1至6天的斑马鱼胚胎/幼体中表征10个神经系统基因的发育表达谱。突触蛋白Ⅱ a（syn 2a）和髓鞘碱性蛋白（mbp）的转录在整个发育过程中增加，而gap 43、elavl 3、nkx 22 a、神经生成素1（ngn 1）、α 1-微管蛋白和胶质细胞酸性蛋白（gfap）的转录最初增加，但随后下降。巢蛋白和音速刺猬a（shha）的转录本在发育过程中减少。我们测试了这些潜在的生物标志物对发育神经毒物暴露的反应，发现一个基因子集的表达谱在暴露于亚致死剂量的乙醇（一种已知的发育神经毒物）期间和之后都发生了改变。总的来说，这些数据表明，候选基因的转录水平的变化在发展过程中的模式是一致的文献报道，和转录的表达受到干扰的处理与发育神经毒剂（乙醇）。这些结果表明，这些基因的表达谱可能是有用的生物标志物，用于快速评价化学品的发育神经毒性潜力。爱思唯尔公司出版
Hazard information essential to guide developmental neurotoxicity risk assessments is limited for many chemicals. As developmental neurotoxicity testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for rapid toxicity screening. Assessing the developmental neurotoxicity potential of chemicals in a rapid throughput mode will be aided by the identification and characterization of transcriptional biomarkers that can be measured accurately and rapidly. To this end, the developmental expression profiles of ten nervous system genes were characterized in 1 to 6 days post fertilization zebrafish embryos/larvae using quantitative real time PCR (qRT-PCR). Transcripts of synapsinII a (syn2a) and myelin basic protein (mbp) increased throughout development, while transcripts of gap43, elavl3, nkx22a, neurogenin 1 (ngn 1), alpha 1-tubulin, and glial fibrillary acidic protein (gfap) initially increased, but subsequently declined. Transcripts for nestin and sonic hedgehog a (shha) decreased during development. We tested the responses of these potential biomarkers to developmental neurotoxicant exposure, and found that the expression profiles of a subset of genes were altered both during and after exposure to sublethal doses of ethanol, a known developmental neurotoxicant. Collectively, these data indicate that transcript levels of the candidate genes change during development in patterns which are consistent with literature reports, and that the expression of the transcripts is perturbed by treatment with a developmental neurotoxicant (ethanol). These results suggest that the expression profiles of these genes may be useful biomarkers for rapid evaluation of the developmental neurotoxicity potential of chemicals. Published by Elsevier Inc.