Presentations

Abstract

Introduction: Epilepsy is one of the most prevalent neurological disorders, characterized by recurring spontaneous seizures. These seizures result from uncontrolled and excessively synchronized neural activity and are the primary manifestation of epilepsy. Although antiseizure medications (ASMs) are effective in controlling seizures, there remains no fully effective therapy for epilepsy, highlighting the urgent need for new treatments with minimal side effects. Current ASMs, while attenuating seizure activity, often come with adverse effects and do not provide a complete cure. The first step in drug discovery for epilepsy involves evaluating potential candidates in preclinical in vitro and in vivo models to assess their susceptibility to seizures. This process is complex, requiring substantial infrastructure, specialized tools, and significant expenses. Traditional models used in this process, such as murine models, are costly and resource intensive. To address these challenges, we identified Dugesia dorotocephala, a species of planarian worm, as a potential invertebrate model for epilepsy research. Planarians possess neural structures that share similarities with vertebrate systems, making them suitable for screening compounds that may affect neural activity and seizure susceptibility. This study aimed to evaluate whether Dugesia dorotocephala could serve as a viable model for studying acute seizures and contribute to the identification and development of new ASMs.

Methods: Planarians (Dugesia dorotocephala) were placed in separated wells and exposed to different concentrations of pilocarpine solutions to induce seizure-like behaviors. Video-recording system were used to record spontaneous and induced behavior. To evaluate behavior responses against ASMs, planarians were subsequently exposed to pilocarpine followed by increasing concentrations of lamotrigine (ASM, blocks sodium channels, and expressed in planarias). The behavioral responses were analyzed using automatic video tracking software and quantified based on parameters shape, motility, frequency, duration, and rotation direction. In addition, the morphology of the nerve fibers was analyzed using Golgi staining and immunohistofluorescence techniques and analysis using cell profile and Image J programs.

Results: The study identified six distinct behavioral phenotypes in response to pilocarpine, with ODE being the most prominent and increasing in frequency in a dose-dependent manner: oscillating dorsal expansion (ODE), head and tail dorsal expansion, C-shape, head flick, and tail flick. lamotrigine mainly at doses 4 and 6mM resulted in a significant attenuation of ODE and other seizure-like behaviors. Preliminary neurohistological analysis revealed nerve damage in pilocarpine-exposed planarians but is preserved after lamotrigine treatment.

Conclusion: The findings of this study support the use of Dugesia dorotocephala as a model for studying acute seizures and screening potential ASMs. The planarian model not only offers a cost-effective alternative to traditional vertebrate models but also provides valuable insights into the neural mechanisms underlying seizure activity. Further histological and genetic studies are recommended to fully explore the potential of Dugesia dorotocephala in the development of therapeutic interventions for epilepsy in humans.