Reference : Cross-species pharmacological characterization of the allylglycine seizure model in m...
Scientific journals : Article
Human health sciences : Multidisciplinary, general & others
Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish.
Leclercq, Karine [> >]
Afrikanova, Tatiana [> >]
Langlois, Melanie [> >]
De Prins, An [> >]
Buenafe, Olivia E. [> >]
Rospo, Chiara C. [> >]
Van Eeckhaut, Ann [> >]
de Witte, Peter A. M. [> >]
Crawford, Alexander Dettmar mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Smolders, Ilse [> >]
Esguerra, Camila V. [> >]
Kaminski, Rafal M. [> >]
Epilepsy & behavior : E&B
Yes (verified by ORBilu)
United States
[en] Allylglycine ; Animals ; Anticonvulsants/therapeutic use ; Diazepam/therapeutic use ; Disease Models, Animal ; Fructose/analogs & derivatives/therapeutic use ; Male ; Mice ; Phenytoin/therapeutic use ; Piracetam/analogs & derivatives/therapeutic use ; Seizures/chemically induced/drug therapy ; Treatment Outcome ; Valproic Acid/therapeutic use ; Zebrafish ; Allylglycine ; Antiepileptic drugs ; Epilepsy ; Seizures ; Treatment resistance ; Zebrafish
[en] 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 gamma-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.
Copyright (c) 2015 Elsevier Inc. All rights reserved.

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