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

Laura Guzman, Gisela Besa, Daniela Linares, Lara González, Caterina Pont, Manuela Bartolini, Ann Cathrin Haigis, Jessica Legradi, Diego Muñoz-Torrero, Jesús Gómez-Catalán, Marta Barenys*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number145
Pages (from-to)1-12
Number of pages12
JournalEnvironmental Sciences Europe
Volume32
Issue number1
Early online date28 Oct 2020
DOIs
Publication statusPublished - 1 Dec 2020

Keywords

  • Alternative organism
  • Behaviour
  • Developmental neurotoxicity
  • Drug screening
  • Methodology
  • Neuromotor
  • Zebrafish

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