PUBLICATION
Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish
- Authors
- Leclercq, K., Afrikanova, T., Langlois, M., De Prins, A., Buenafe, O.E., Rospo, C.C., Van Eeckhaut, A., de Witte, P.A., Crawford, A.D., Smolders, I., Esguerra, C.V., Kaminski, R.M.
- ID
- ZDB-PUB-150408-15
- Date
- 2015
- Source
- Epilepsy & behavior : E&B 45: 53-63 (Journal)
- Registered Authors
- Buenafe, Olivia Erin, Crawford, Alexander, de Witte, Peter, Esguerra, Camila V.
- Keywords
- Allylglycine, Antiepileptic drugs, Epilepsy, Seizures, Treatment resistance, Zebrafish
- MeSH Terms
-
- Allylglycine*
- Animals
- Anticonvulsants/therapeutic use*
- Diazepam/therapeutic use
- Disease Models, Animal*
- Fructose/analogs & derivatives
- Fructose/therapeutic use
- Male
- Mice
- Phenytoin/therapeutic use
- Piracetam/analogs & derivatives
- Piracetam/therapeutic use
- Seizures/chemically induced
- Seizures/drug therapy*
- Treatment Outcome
- Valproic Acid/therapeutic use
- Zebrafish
- PubMed
- 25845493 Full text @ Epilepsy Behav.
Citation
Leclercq, K., Afrikanova, T., Langlois, M., De Prins, A., Buenafe, O.E., Rospo, C.C., Van Eeckhaut, A., de Witte, P.A., Crawford, A.D., Smolders, I., Esguerra, C.V., Kaminski, R.M. (2015) Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish. Epilepsy & behavior : E&B. 45:53-63.
Abstract
Treatment-resistant seizures affect about a third of patients suffering from epilepsy. To fulfill the need for new medications targeting treatment-resistant seizures, a number of rodent models offer the opportunity to assess a variety of potential treatment approaches. The use of such models, however, has proven to be time-consuming and labor-intensive. In this study, we performed pharmacological characterization of the allylglycine (AG) seizure model, a simple in vivo model for which we demonstrated a high level of treatment resistance. (d,l)-Allylglycine inhibits glutamic acid decarboxylase (GAD) - the key enzyme in γ-aminobutyric acid (GABA) biosynthesis - leading to GABA depletion, seizures, and neuronal damage. We performed a side-by-side comparison of mouse and zebrafish acute AG treatments including biochemical, electrographic, and behavioral assessments. Interestingly, seizure progression rate and GABA depletion kinetics were comparable in both species. Five mechanistically diverse antiepileptic drugs (AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and topiramate) showed only a limited protective effect (mainly mortality delay) at doses close to the TD50 (dose inducing motor impairment in 50% of animals) in mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective activity against AG-induced seizures. Experiments performed in zebrafish larvae revealed behavioral AED activity profiles highly analogous to those obtained in mice. Having demonstrated cross-species similarities and limited efficacy of tested AEDs, we propose the use of AG in zebrafish as a convenient and high-throughput model of treatment-resistant seizures.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping