RRC ID 59939
Author Brenet A, Hassan-Abdi R, Somkhit J, Yanicostas C, Soussi-Yanicostas N.
Title Defective Excitatory/Inhibitory Synaptic Balance and Increased Neuron Apoptosis in a Zebrafish Model of Dravet Syndrome.
Journal 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.
Volume 8(10)
Published 2019-10-4
DOI 10.3390/cells8101199
PII cells8101199
PMID 31590334
PMC PMC6829503
MeSH 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
IF 5.656
Times Cited 3
Zebrafish Tg(vglut2a:loxP-DsRed-loxP-GFP) Tg(gad1b:GFP)