Abstract：
We have adapted a semiautomated method for tracking Caenorhabditis elegans spontaneous locomotor activity into a quantifiable assay by developing a sophisticated method for analyzing the time course of measured activity. The 16-h worm Adult Activity Test (wAAT) can be used to measure C. elegans activity levels for efficient screening for pharmacological and toxicity-induced effects. As with any apical endpoint assay, the wAAT is mode of action agnostic, allowing for detection of effects from a broad spectrum of response pathways. With caffeine as a model mild stimulant, the wAAT showed transient hyperactivity followed by reversion to baseline. Mercury chloride (HgCl2 ) produced an early dose-response hyperactivity phase followed by pronounced hypoactivity, a behavior pattern we have termed a toxicant \"escape response.\" Methylmercury chloride (meHgCl) produced a similar pattern to HgCl2 , but at much lower concentrations, a weaker hyperactivity response, and more pronounced hypoactivity. Sodium arsenite (NaAsO2 ) and dimethylarsinic acid (DMA) induced hypoactivity at high concentrations. Acute toxicity, as measured by hypoactivity in C. elegans adults, was ranked: meHgCl > HgCl2 > NaAsO2 = DMA. Caffeine was not toxic with the wAAT at tested concentrations. Methods for conducting the wAAT are described, along with instructions for preparing C. elegans Habitation Medium, a liquid nutrient medium that allows for developmental timing equivalent to that found with C. elegans grown on agar with OP50 Escherichia coli feeder cultures. A de novo mathematical parametric model for adult C. elegans activity and the application of this model in ranking exposure toxicity are presented.
摘要：
通过开发一种复杂的分析方法来分析测得的活动的时间过程，我们已将一种用于跟踪秀丽隐杆线虫自发运动活动的半自动方法调整为可量化的测定。16小时蠕虫成虫活性测试（wAAT）可用于测量秀丽隐杆线虫的活性水平，以有效筛选药理学和毒性诱导的作用。与任何顶端终点测定一样，WAAT是不可知的动作模式，允许检测来自广谱响应途径的效应。咖啡因作为一种温和的兴奋剂，wAAT显示短暂性多动症,随后回复至基线.氯化汞（HgCl2）产生了早期的剂量反应多动期，然后是明显的低活动，一种我们称之为有毒物质“逃避反应”的行为模式。“氯化甲基汞（meHgCl）产生与HgCl2相似的模式，但是在更低的浓度下，较弱的多动反应，和更明显的缺乏活力。亚砷酸钠（NaAsO2）和二甲基arsinic酸（DMA）在高浓度下会引起活动不足。急性毒性,以秀丽隐杆线虫成虫的活动不足来衡量，排序为：meHgCl>HgCl2>NaAsO2=DMA。咖啡因在测试浓度下对wAAT没有毒性。描述了用于进行WAAT的方法，以及准备C.elegansHabitationMedium的说明，一种液体营养培养基，其发育时间与在具有OP50大肠杆菌饲养培养物的琼脂上生长的秀丽隐杆线虫相同。提出了成年秀丽隐杆线虫活性的从头数学参数模型以及该模型在对暴露毒性进行排名中的应用。
