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快速斑马鱼行为分析检测法加速环境神经发育毒性剂的鉴定。

Rapid Zebrafish Behavioral Profiling Assay Accelerates the Identification of Environmental Neurodevelopmental Toxicants.

机构信息

School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, Massachusetts 02115, United States.

出版信息

Environ Sci Technol. 2021 Feb 2;55(3):1919-1929. doi: 10.1021/acs.est.0c06949. Epub 2021 Jan 20.

DOI:10.1021/acs.est.0c06949
PMID:33470099
Abstract

Rapid and cost-effective assays to screen potential environmental neurodevelopmental toxicants are necessary to address the limitations of platforms, such as the inability to fully recapitulate the developmental and physiological processes of whole organisms. In the present study, a rapid zebrafish behavioral profiling assay was developed to characterize the neurodevelopmental effects of environmental substances by quantitatively evaluating multiple spontaneous movement features of zebrafish embryos. This video analysis-based assay automatically segmented every embryo and thus was able to accurately quantify spontaneous movement features, including frequency, duration, intensity, interval, and the number of continuous movements. When tested with eight environmental substances known to be neurodevelopmental toxicants, such as chlorpyrifos and bisphenol A, the assay successfully captured frequency alterations that were well-documented in previous studies while also providing additional information. Using an optimized procedure, we further assessed 132 potential neurotoxins that spanned a wide range of molecular targets, many of which were previously detected in environmental waterbodies. The distinct altered behavioral barcodes indicated that the spontaneous movement was impacted by diverse neuroactive substances, and the effects could be effectively evaluated with the developed assay. The web-based tool, named EMAnalysis, is further provided at http://www.envh.sjtu.edu.cn/zebrafish_contraction.jsp. Thus, this assay provides an efficient platform to accelerate the pace of neurotoxic environmental contaminant discoveries.

摘要

快速且经济高效的检测方法,用于筛选潜在的环境神经发育毒性物质,对于解决平台的局限性是必要的,例如无法充分模拟整个生物体的发育和生理过程。在本研究中,开发了一种快速的斑马鱼行为分析检测方法,通过定量评估斑马鱼胚胎的多个自发运动特征,来描述环境物质的神经发育影响。这种基于视频分析的检测方法自动分割每个胚胎,因此能够准确地量化自发运动特征,包括频率、持续时间、强度、间隔和连续运动的数量。当用已知具有神经发育毒性的八种环境物质(如毒死蜱和双酚 A)进行测试时,该检测方法成功地捕捉到了以前研究中记录的频率变化,同时还提供了其他信息。使用优化的程序,我们进一步评估了 132 种潜在的神经毒素,这些毒素涵盖了广泛的分子靶标,其中许多在以前的环境水体中被检测到。独特的改变行为条形码表明,自发运动受到多种神经活性物质的影响,并且可以使用开发的检测方法有效地评估这些影响。名为 EMAnalysis 的网络工具进一步在 http://www.envh.sjtu.edu.cn/zebrafish_contraction.jsp 提供。因此,该检测方法为加速神经毒性环境污染物的发现提供了一个高效的平台。

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