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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Methods and Model Organisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1418606
This article is part of the Research Topic Multi-modality tools and applications in functional and mechanistic exploration in nervous systems View all 3 articles

Induction of seizures and initiation of epileptogenesis by pilocarpine in zebrafish larvae

Provisionally accepted
Kinga A. Gawel Kinga A. Gawel 1*Monika Hulas-Stasiak Monika Hulas-Stasiak 2Marta Marszalek-Grabska Marta Marszalek-Grabska 1Anna Grenda Anna Grenda 1Aleksandra Siekierska Aleksandra Siekierska 3Nataliia Kosheva Nataliia Kosheva 1Wietske van der Ent Wietske van der Ent 4Camila V. Esguerra Camila V. Esguerra 4Pawel Krawczyk Pawel Krawczyk 1Waldemar A. Turski Waldemar A. Turski 1
  • 1 Medical University of Lublin, Lublin, Poland
  • 2 Marie Curie-Sklodowska University, Lublin, Lublin Voivodeship, Poland
  • 3 KU Leuven, Leuven, Belgium
  • 4 University of Oslo, Oslo, Oslo, Norway

The final, formatted version of the article will be published soon.

    Objective: Preclinical models of seizures and epilepsy in rodents contributed substantially to the discovery of currently available antiseizure medications. These were also broadly used for investigation of processes of epileptogenesis. Nevertheless, rodent models pose some limitations, thus, new models using alternative species are in high demand. The aim of this study was to describe a new model of seizures/epilepsy induced by the cholinomimetic agent, pilocarpine (PILO), in larval zebrafish.: Local field potential (LFP) recordings were conducted to analyze electroencephalographic discharges and correlate it with larval behavior. Hematoxylin and eosin staining, as well as TUNEL staining were performed to analyze morphology and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was undertaken for gene expression analysis.Results: Acute exposure to PILO, in a concentration-dependent manner, induces electroencephalographic discharges in larval zebrafish, which behaviorally manifest as decreased locomotion and moving time, but enhanced movement velocity. The PILO-induced seizure-like activity is behaviorally distinct from this induced by the application of chemoconvulsant pentylenetetrazole (PTZ). Zebrafish larvae previously exposed to PILO (2 h), after a washing out period, exhibit spontaneous, unprovoked discharges and apoptotic changes in their brains.Significance: Here, we comprehensively investigated a new model of PILO-induced seizures/epilepsy in larval zebrafish. We propose that this model may be used to study epileptogenesis and for antiseizure drug screening purposes.

    Keywords: Zebrafish, Pilocarpine, seizure, Epileptogenesis, locomotor activity, local field potential recordings

    Received: 16 Apr 2024; Accepted: 19 Jun 2024.

    Copyright: © 2024 Gawel, Hulas-Stasiak, Marszalek-Grabska, Grenda, Siekierska, Kosheva, van der Ent, Esguerra, Krawczyk and Turski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kinga A. Gawel, Medical University of Lublin, Lublin, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.