Neurotoxicity assessment using zebrafish
Neurotoxicity assessment using zebrafish
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DOI：
10.1016/j.vascn.2006.04.004
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发表时间：
2007-01-01
影响因子：
1.9
通讯作者：
McGrath, Patricia
中科院分区：
文献类型：
--
作者：
Parng, Chuenlei;Roy, Nicole Marie;McGrath, Patricia
简介：透明是斑马鱼的独特属性，允许使用全挂载抗体免疫染色和组织化学直接评估药物对神经系统的作用。方法：采用全载免疫染色法观察不同类型的神经细胞，观察药物对视神经、运动神经元和多巴胺能神经元的药理作用。此外，我们还利用TUNEL染色、免疫染色和原位杂交技术评估了神经元凋亡、增殖、氧化和髓鞘的完整性。检测多巴胺能神经元的数量，并进行形态学分析，量化髓鞘碱性蛋白和细胞凋亡的染色信号。结果：我们发现在人类中引起神经毒性的化合物在斑马鱼中引起类似的神经毒性。例如，乙醇诱导视神经和运动神经元缺损，影响神经元增殖；6-羟多巴胺引起神经元氧化和多巴胺能神经元损失；丙烯酰胺诱导脱髓鞘；紫杉醇、新霉素、TCDD和维甲酸诱导神经元凋亡。讨论：在完整的动物中，药物治疗对不同神经元的影响可以很容易地进行视觉评估和量化。这些结果支持使用斑马鱼作为评估神经毒性的预测模型。(c) 2006爱思唯尔公司版权所有。
Introduction: Transparency is a unique attribute of zebrafish that permits direct assessment of drug effects on the nervous system using whole mount antibody immunostaining and histochemistry. Methods: To assess pharmacological effects of drugs on the optic nerves, motor neurons, and dopaminergic neurons, we performed whole mount immunostaining and visualized different neuronal cell types in vivo. In addition, we assessed neuronal apoptosis, proliferation, oxidation and the integrity of the myelin sheath using TUNEL staining, immunostaining and in situ hybridization. The number of dopaminergic neurons was examined and morphometric analysis was performed to quantify the staining signals for myelin basic protein and apoptosis. Results: We showed that compounds that induce neurotoxicity in humans caused similar neurotoxicity in zebrafish. For example, ethanol induced defects in optic nerves and motor neurons and affected neuronal proliferation; 6-hydroxydopamine caused neuronal oxidation and dopaminergic neuron loss; acrylamide induced demyelination; taxol, neomycin, TCDD and retinoic acid induced neuronal apoptosis. Discussion: Effects of drug treatment on different neurons can easily be visually assessed and quantified in intact animals. These results support the use of zebrafish as a predictive model for assessing neurotoxicity. (c) 2006 Elsevier Inc. All rights reserved.