Background

The difficulty of finding new treatments for neurological diseases with great impact in our society like Alzheimer’s disease can be ascribed in part to the complexity of the nervous system and the lack of quick and cost-effective screening tools. Such tools could not only help to identify potential novel treatments, but could also be used to test environmental contaminants for their potential to cause neurotoxicity. It has been estimated that 5–10% of the anthropogenic chemicals are developmental neurotoxic (DNT) and exposure to DNT compounds has been linked to several neurological diseases. Within this study we were testing the applicability of a quick and cost-effective behavioural test using zebrafish embryos: the touch-evoked response assay, in this case, an assay evaluating the swimming response to a tap in the tail. Two acetylcholinesterase (AChE) inhibitors positive controls (paraoxon and huprine Y), as well as 10 huprine-derivative compounds were tested and the results were evaluated using 2 different methods, a quantitative and a qualitative one.

Results

We could show that the methodology presented is able to detect behavioural effects of AChE inhibitors. A good correlation between the results obtained with the quantitative and the qualitative method was obtained (R² = 0.84).

Conclusions

Our proposed method enables combination of screening for new drugs with toxicity screening in a whole embryo model alternative to animal experimentation, thereby merging 2 drug development steps into one.

中文翻译：

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评估乙酰胆碱酯酶抑制剂在斑马鱼触摸诱发反应中的作用：定量与定性评估

背景

寻找对像阿尔茨海默氏病这样对我们社会有重大影响的神经系统疾病的新疗法的困难，部分原因在于神经系统的复杂性以及缺乏快速且经济高效的筛查工具。这样的工具不仅可以帮助确定潜在的新颖疗法，还可以用于测试环境污染物引起神经毒性的潜力。据估计，5–10％的人为化学物质是发育性神经毒性（DNT），接触DNT化合物与几种神经系统疾病有关。在这项研究中，我们正在测试使用斑马鱼胚胎进行的快速且具有成本效益的行为测试的适用性：触摸诱发反应测定，在这种情况下，是一种评估对尾巴轻拍的游泳反应的测定。

结果

我们可以证明所提出的方法能够检测AChE抑制剂的行为影响。用定量和定性方法获得的结果之间具有良好的相关性（R ²  = 0.84）。

结论

我们提出的方法可以在整个胚胎模型中将新药的筛选与毒性筛选相结合，从而替代动物实验，从而将2个药物开发步骤合并为一个。