Effects of Diazepam on Gene Expression and Link to Physiological Effects in Different Life Stages in Zebrafish Danio rerio
Effects of Diazepam on Gene Expression and Link to Physiological Effects in Different Life Stages in Zebrafish Danio rerio
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DOI：
10.1021/es100980r
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发表时间：
2010-10-01
影响因子：
11.4
通讯作者：
Fent, Karl
中科院分区：
文献类型：
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作者：
Oggier, Daniela M.;Weisbrod, Christin I.;Fent, Karl
我们应用斑马鱼全基因组微阵列来识别地西泮（一种在废水污染环境中遇到的神经药物）的分子效应，并阐明其神经毒性作用模式。进行行为研究来分析改变的基因表达与对有机体水平的影响之间的相关性。雄性斑马鱼和斑马鱼刺五加胚胎在孵化后分别暴露于标称水平 273 ng/L 和 273 mu g/L（成年实验中测定的水浓度为 235 ng/L 和 291 mu g/L）。微阵列和定量 PCR 均显示，在两个浓度下分别有 51 个和 103 个改变的转录本中，成年斑马鱼和刺五加胚胎中涉及昼夜节律的基因的表达具有特别重要的意义。刺五加胚胎的游泳行为在 273 μg/L 时显着改变。该研究得出的结论是，地西泮引起的昼夜节律相关基因的改变与地西泮高浓度下神经行为的影响是平行的，但在污染环境中可能发生的低地西泮浓度下则不然。
We applied zebrafish whole genome microarrays to identify molecular effects of diazepam, a neuropharmaceutical encountered in wastewater-contaminated environments, and to elucidate its neurotoxic mode of action. Behavioral studies were performed to analyze for correlations between altered gene expression with effects on the organism level. Male zebrafish and zebrafish eleuthero-embryos were exposed for 14 d or up to 3 d after hatching, respectively, to nominal levels of 273 ng/L and 273 mu g/L (determined water concentrations in the adult experiment 235 ng/L and 291 mu g/L). Among the 51 and 103 altered transcripts at both concentrations, respectively, the expression of genes involved in the circadian rhythm in adult zebrafish and eleuthero-embryos were of particular significance, as revealed both by microarrays and quantitative PCR. The swimming behavior of eleuthero-embryos was significantly altered at 273 mu g/L. The study leads to the conclusion that diazepam-induced alterations of genes involved in circadian rhythm are paralleled by effects in neurobehavior at high, but not at low diazepam concentrations that may occur in polluted environments.