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斑马鱼模型中测试环境污染物神经毒性的方法:从行为到分子机制

Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms.

作者信息

Fitzgerald Jennifer A, Könemann Sarah, Krümpelmann Laura, Županič Anže, Vom Berg Colette

机构信息

Eawag, Swiss Federal Institute of Aquatic Science and Technology, Dübendorf, Switzerland.

EPF Lausanne, School of Architecture, Civil and Environmental Engineering, Lausanne, Switzerland.

出版信息

Environ Toxicol Chem. 2021 Apr;40(4):989-1006. doi: 10.1002/etc.4951. Epub 2021 Feb 1.

DOI:10.1002/etc.4951
PMID:33270929
Abstract

The occurrence of neuroactive chemicals in the aquatic environment is on the rise and poses a potential threat to aquatic biota of currently unpredictable outcome. In particular, subtle changes caused by these chemicals to an organism's sensation or behavior are difficult to tackle with current test systems that focus on rodents or with in vitro test systems that omit whole-animal responses. In recent years, the zebrafish (Danio rerio) has become a popular model organism for toxicological studies and testing strategies, such as the standardized use of zebrafish early life stages in the Organisation for Economic Co-operation and Development's guideline 236. In terms of neurotoxicity, the zebrafish provides a powerful model to investigate changes to the nervous system from several different angles, offering the ability to tackle the mechanisms of action of chemicals in detail. The mechanistic understanding gained through the analysis of this model species provides a good basic knowledge of how neuroactive chemicals might interact with a teleost nervous system. Such information can help infer potential effects occurring to other species exposed to neuroactive chemicals in their aquatic environment and predicting potential risks of a chemical for the aquatic ecosystem. In the present article, we highlight approaches ranging from behavioral to structural, functional, and molecular analysis of the larval zebrafish nervous system, providing a holistic view of potential neurotoxic outcomes. Environ Toxicol Chem 2021;40:989-1006. © 2020 SETAC.

摘要

神经活性化学物质在水生环境中的出现呈上升趋势,对水生生物群构成了目前结果难以预测的潜在威胁。特别是,这些化学物质对生物体感觉或行为造成的细微变化,难以通过当前专注于啮齿动物的测试系统或忽略全动物反应的体外测试系统来解决。近年来,斑马鱼(Danio rerio)已成为毒理学研究和测试策略的常用模式生物,例如经济合作与发展组织准则236中斑马鱼早期生命阶段的标准化使用。在神经毒性方面,斑马鱼提供了一个强大的模型,可从几个不同角度研究神经系统的变化,能够详细探讨化学物质的作用机制。通过对这种模式物种的分析获得的机制理解,为神经活性化学物质如何与硬骨鱼神经系统相互作用提供了良好的基础知识。这些信息有助于推断在水生环境中接触神经活性化学物质的其他物种可能出现的潜在影响,并预测化学物质对水生生态系统的潜在风险。在本文中,我们重点介绍了从行为到幼虫斑马鱼神经系统的结构、功能和分子分析等方法,提供了潜在神经毒性结果的整体视图。《环境毒理学与化学》2021年;40:989 - 1006。© 2020 SETAC。

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