PUBLICATION

Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome

Authors
Brenet, A., Hassan-Abdi, R., Somkhit, J., Yanicostas, C., Soussi-Yanicostas, N.
ID
ZDB-PUB-191011-2
Date
2019
Source
Cells   8(10): (Journal)
Registered Authors
Soussi-Yanicostas, Nadia
Keywords
Apoptosis, Calcium imaging, Dravet syndrome, Excitatory/inhibitory balance, In vivo imaging, Local field potential, Morpholino scn1LabAUG, Zebrafish, scn1Lab
MeSH Terms
  • Animals
  • Apoptosis*
  • Calcium/metabolism
  • Disease Models, Animal
  • Epilepsies, Myoclonic/genetics
  • Epilepsies, Myoclonic/pathology*
  • Epilepsies, Myoclonic/physiopathology*
  • Excitatory Postsynaptic Potentials*
  • Inhibitory Postsynaptic Potentials*
  • Neurons/pathology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
PubMed
31590334 Full text @ Cells
Abstract
Dravet syndrome is a type of severe childhood epilepsy that responds poorly to current anti-epileptic drugs. In recent years, zebrafish disease models with Scn1Lab sodium channel deficiency have been generated to seek novel anti-epileptic drug candidates, some of which are currently undergoing clinical trials. However, the spectrum of neuronal deficits observed following Scn1Lab depletion in zebrafish larvae has not yet been fully explored. To fill this gap and gain a better understanding of the mechanisms underlying neuron hyperexcitation in Scn1Lab-depleted larvae, we analyzed neuron activity in vivo using combined local field potential recording and transient calcium uptake imaging, studied the distribution of excitatory and inhibitory synapses and neurons as well as investigated neuron apoptosis. We found that Scn1Lab-depleted larvae displayed recurrent epileptiform seizure events, associating massive synchronous calcium uptakes and ictal-like local field potential bursts. Scn1Lab-depletion also caused a dramatic shift in the neuronal and synaptic balance toward excitation and increased neuronal death. Our results thus provide in vivo evidence suggesting that Scn1Lab loss of function causes neuron hyperexcitation as the result of disturbed synaptic balance and increased neuronal apoptosis.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes