Evaluation of the effects of acetylcholinesterase inhibitors in the zebrafish touch-evoked response: quantitative vs. qualitative assessment

Environmental Sciences Europe

Manuela Bartolini¹  Daniela Linares²  Laura Guzman²  Gisela Besa²  Lara González²  Jesús Gómez-Catalán³  Marta Barenys³  Ann-Cathrin Haigis⁴  Jessica Legradi⁵  Diego Muñoz-Torrero⁶  Caterina Pont⁶ 

[1] Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy;GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, Barcelona, Spain;GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII 27-31, Barcelona, Spain;Institute of Nutrition Research and Food Safety (INSA-UB), University of Barcelona, Barcelona, Spain;Institute for Environmental Research, RWTH Aachen University, Aachen, Germany;Institute for Environmental Studies, VU University, Amsterdam, The Netherlands;Laboratory of Medicinal Chemistry (CSIC Associated Unit), Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain;

关键词: Behaviour;    Neuromotor;    Developmental neurotoxicity;    Alternative organism;    Methodology;    Zebrafish;    Drug screening;   

DOI  :  10.1186/s12302-020-00421-7

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsWe 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).ConclusionsOur 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.

【 授权许可】

CC BY