The fruit fly Drosophila melanogaster as a screening model for antiseizure medications
ObjectiveResistance to antiseizure medications (ASMs) is a major challenge in the treatment of patients with epilepsy. Despite numerous newly marketed ASMs, the proportion of drug-resistant people with epilepsy has not significantly decreased over the years. Therefore, novel and innovative seizure m...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1489888/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846129510962954240 |
|---|---|
| author | Florian P. Fischer Robin A. Karge Henner Koch Aaron Voigt Aaron Voigt Yvonne G. Weber Stefan Wolking |
| author_facet | Florian P. Fischer Robin A. Karge Henner Koch Aaron Voigt Aaron Voigt Yvonne G. Weber Stefan Wolking |
| author_sort | Florian P. Fischer |
| collection | DOAJ |
| description | ObjectiveResistance to antiseizure medications (ASMs) is a major challenge in the treatment of patients with epilepsy. Despite numerous newly marketed ASMs, the proportion of drug-resistant people with epilepsy has not significantly decreased over the years. Therefore, novel and innovative seizure models for preclinical drug screening are highly desirable. Here, we explore the efficacy of a broad spectrum of ASMs in suppressing seizure activity in two established Drosophila melanogaster bang-sensitive mutants. These mutants respond with seizures to mechanical stimulation, providing a promising platform for screening novel ASMs.MethodsSeven frequently used ASMs (brivaracetam, cenobamate, lacosamide, lamotrigine, levetiracetam, phenytoin, and valproate) were administered to the bang-sensitive mutants easily shocked2F (eas2F) and paralyticbss1 (parabss1). After 48 h of treatment, the flies were vortexed to induce mechanical stimulation. The seizure probability (i.e., ratio of seizing and non-seizing flies) as well as the seizure duration were analyzed.ResultsIn case of eas2F mutants, treatment with the sodium channel blockers phenytoin and lamotrigine resulted in a robust reduction of seizure probability, whereas flies treated with lacosamide showed a decrease in seizure duration. Treatment with valproate resulted in both a reduction in seizure probability and in seizure duration. In contrast, levetiracetam, brivaracetam and cenobamate had no effect on the bang-sensitive phenotype of eas2F flies. In case of parabss1 flies, none of the tested medications significantly reduced seizure activity, supporting its role as a model of intractable epilepsy.SignificanceOur results show that particularly sodium channel blockers as well as valproate are effective in suppressing seizure activity in the bang-sensitive mutant eas2F. These findings demonstrate the usability of Drosophila for screening drugs with antiseizure properties. Due to fewer ethical concerns, the short life cycle, and low maintenance costs, Drosophila might provide an attractive and innovative high-throughput model for the discovery of novel antiseizure compounds. |
| format | Article |
| id | doaj-art-0444e4f7f30d48b197d58b8fca697e4c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-0444e4f7f30d48b197d58b8fca697e4c2024-12-10T04:25:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-12-011510.3389/fphar.2024.14898881489888The fruit fly Drosophila melanogaster as a screening model for antiseizure medicationsFlorian P. Fischer0Robin A. Karge1Henner Koch2Aaron Voigt3Aaron Voigt4Yvonne G. Weber5Stefan Wolking6Department of Epileptology and Neurology, RWTH Aachen University, Aachen, GermanyDepartment of Epileptology and Neurology, RWTH Aachen University, Aachen, GermanyDepartment of Epileptology and Neurology, RWTH Aachen University, Aachen, GermanyDepartment of Neurology, RWTH Aachen University, Aachen, GermanyJARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, Aachen, GermanyDepartment of Epileptology and Neurology, RWTH Aachen University, Aachen, GermanyDepartment of Epileptology and Neurology, RWTH Aachen University, Aachen, GermanyObjectiveResistance to antiseizure medications (ASMs) is a major challenge in the treatment of patients with epilepsy. Despite numerous newly marketed ASMs, the proportion of drug-resistant people with epilepsy has not significantly decreased over the years. Therefore, novel and innovative seizure models for preclinical drug screening are highly desirable. Here, we explore the efficacy of a broad spectrum of ASMs in suppressing seizure activity in two established Drosophila melanogaster bang-sensitive mutants. These mutants respond with seizures to mechanical stimulation, providing a promising platform for screening novel ASMs.MethodsSeven frequently used ASMs (brivaracetam, cenobamate, lacosamide, lamotrigine, levetiracetam, phenytoin, and valproate) were administered to the bang-sensitive mutants easily shocked2F (eas2F) and paralyticbss1 (parabss1). After 48 h of treatment, the flies were vortexed to induce mechanical stimulation. The seizure probability (i.e., ratio of seizing and non-seizing flies) as well as the seizure duration were analyzed.ResultsIn case of eas2F mutants, treatment with the sodium channel blockers phenytoin and lamotrigine resulted in a robust reduction of seizure probability, whereas flies treated with lacosamide showed a decrease in seizure duration. Treatment with valproate resulted in both a reduction in seizure probability and in seizure duration. In contrast, levetiracetam, brivaracetam and cenobamate had no effect on the bang-sensitive phenotype of eas2F flies. In case of parabss1 flies, none of the tested medications significantly reduced seizure activity, supporting its role as a model of intractable epilepsy.SignificanceOur results show that particularly sodium channel blockers as well as valproate are effective in suppressing seizure activity in the bang-sensitive mutant eas2F. These findings demonstrate the usability of Drosophila for screening drugs with antiseizure properties. Due to fewer ethical concerns, the short life cycle, and low maintenance costs, Drosophila might provide an attractive and innovative high-throughput model for the discovery of novel antiseizure compounds.https://www.frontiersin.org/articles/10.3389/fphar.2024.1489888/fullanimal modelantiseizure medicationsDrosophila melanogasterdrug screeningepilepsyseizure model |
| spellingShingle | Florian P. Fischer Robin A. Karge Henner Koch Aaron Voigt Aaron Voigt Yvonne G. Weber Stefan Wolking The fruit fly Drosophila melanogaster as a screening model for antiseizure medications Frontiers in Pharmacology animal model antiseizure medications Drosophila melanogaster drug screening epilepsy seizure model |
| title | The fruit fly Drosophila melanogaster as a screening model for antiseizure medications |
| title_full | The fruit fly Drosophila melanogaster as a screening model for antiseizure medications |
| title_fullStr | The fruit fly Drosophila melanogaster as a screening model for antiseizure medications |
| title_full_unstemmed | The fruit fly Drosophila melanogaster as a screening model for antiseizure medications |
| title_short | The fruit fly Drosophila melanogaster as a screening model for antiseizure medications |
| title_sort | fruit fly drosophila melanogaster as a screening model for antiseizure medications |
| topic | animal model antiseizure medications Drosophila melanogaster drug screening epilepsy seizure model |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1489888/full |
| work_keys_str_mv | AT florianpfischer thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT robinakarge thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT hennerkoch thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT aaronvoigt thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT aaronvoigt thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT yvonnegweber thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT stefanwolking thefruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT florianpfischer fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT robinakarge fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT hennerkoch fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT aaronvoigt fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT aaronvoigt fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT yvonnegweber fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications AT stefanwolking fruitflydrosophilamelanogasterasascreeningmodelforantiseizuremedications |