Acute effect of antiseizure drugs on background oscillations in Scn1a A1783V Dravet syndrome mouse model

Shir Quinn, Marina Brusel, Mor Ovadia, Moran Rubinstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. Antiseizure medications (ASMs) for Dravet patients include valproic acid (VA) or clobazam (CLB), with or without stiripentol (STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. In addition to their effect on epileptic phenotypes, ASMs were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alterations in Dravet. Here, utilizing Dravet mice (DS, Scn1aA1783V/WT), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Compared to wild-type mice, background ECoG activity in DS mice had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, VA, CLB, or a combination of CLB + STP, caused, in most mice, a reduction in the frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes, with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Together, these data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations, and highlight a possible correlation between their effect on epilepsy and background activity.

Original languageEnglish
Article number1118216
JournalFrontiers in Pharmacology
Volume14
DOIs
StatePublished - 2023

Funding

FundersFunder number
American Dravet Syndrome Foundation
Claire and Amedee Maratier Institute for the Study of Blindness
Sackler Faculty of Medicine
Stolz Foundation Sackler Faculty of Medicine
Visual Disorders
Israel Science Foundation1454/17
Tel Aviv University

    Keywords

    • Dravet syndrome
    • antiseizure
    • background oscillations
    • mouse model
    • spectral modulation

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