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

Funding

This research was supported by funds from Fundació Bosch i Gimpera (project number FBG-300155) and by Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and FEDER (SAF2017-82771-R) and Generalitat de Catalunya (2017SGR106 and 2017SGR6). ACH was funded by the BMBF project Neurobox (02WRS1419C). A fellowship from Ministerio de Educación, Cultura y Deporte to C.P. is gratefully acknowledged. Acknowledgements

FundersFunder number
Ministerio de Ciencia, Innovación y Universidades
Bundesministerium für Bildung und Forschung02WRS1419C
Generalitat de Catalunya2017SGR106, 2017SGR6
Ministerio de Educación, Cultura y Deporte
Fundació Bosch i GimperaFBG-300155
European Regional Development FundSAF2017-82771-R
Agencia Estatal de Investigación

    Keywords

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

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