PUBLICATION
A zebrafish-centric approach to antiepileptic drug development
- Authors
- Baraban, S.C.
- ID
- ZDB-PUB-210708-4
- Date
- 2021
- Source
- Disease models & mechanisms 14(7): (Other)
- Registered Authors
- Baraban, Scott
- Keywords
- Epilepsy, Perspective, Zebrafish
- MeSH Terms
-
- Animals
- Anticonvulsants/pharmacology
- Anticonvulsants/therapeutic use
- Epilepsy*/drug therapy
- Pentylenetetrazole/therapeutic use
- Seizures/drug therapy
- Seizures/genetics
- Zebrafish*/physiology
- PubMed
- 34231838 Full text @ Dis. Model. Mech.
Citation
Baraban, S.C. (2021) A zebrafish-centric approach to antiepileptic drug development. Disease models & mechanisms. 14(7).
Abstract
Danio rerio (zebrafish) are a powerful experimental model for genetic and developmental studies. Adaptation of zebrafish to study seizures was initially established using the common convulsant agent pentylenetetrazole (PTZ). Larval PTZ-exposed zebrafish exhibit clear behavioral convulsions and abnormal electrographic activity, reminiscent of interictal and ictal epileptiform discharge. By using this model, our laboratory developed simple locomotion-based and electrophysiological assays to monitor and quantify seizures in larval zebrafish. Zebrafish also offer multiple advantages for rapid genetic manipulation and high-throughput phenotype-based drug screening. Combining these seizure assays with genetically modified zebrafish that represent Dravet syndrome, a rare genetic epilepsy, ultimately contributed to a phenotype-based screen of over 3500 drugs. Several drugs identified in these zebrafish screens are currently in clinical or compassionate-use trials. The emergence of this 'aquarium-to-bedside' approach suggests that broader efforts to adapt and improve upon this zebrafish-centric strategy can drive a variety of exciting new discoveries.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping