Journal article
Compensatory rearrangement of parvalbumin interneuron voltage-gated sodium channel subunits in a mouse model of Dravet syndrome
Epilepsia (Copenhagen), Vol.67(8), pp.e133-e140
06/08/2026
DOI: 10.1002/epi.70336
PMCID: PMC13525587
PMID: 42257687
Abstract
Heterozygous loss-of-function variants in the gene SCN1A, which encodes the voltage-gated sodium channel (VGSC) pore-forming (α) subunit NaV1.1, lead to a spectrum of neurological disease, including Dravet syndrome. NaV1.1 is prominently expressed at the proximal portion of the axon initial segment (AIS) of fast-spiking γ-aminobutyric acidergic parvalbumin-expressing inhibitory interneurons (PV+INs). In Dravet syndrome (Scn1a+/− haploinsufficient) mice, action potential firing is impaired in PV+INs during postnatal development; however, in mature animals, PV+IN fast-firing frequency has recovered. We used detailed immunohistochemistry and microscopy to probe the mechanism of this functional recovery, investigating potential upregulation of other brain-expressed VGSC subunits at the PV+IN AIS. We found a specific upregulation of NaV1.6 immunofluorescence at the AIS of PV+INs in adult (but not developing) Scn1a+/− mice compared to wild type, with no upregulation of other brain-expressed subunits NaV1.2 or NaV1.3. These results demonstrate one mechanism through which epilepsy-related gene variants reorganize the developing brain and enact endogenous changes that may be at least partially compensatory.
Details
- Title: Subtitle
- Compensatory rearrangement of parvalbumin interneuron voltage-gated sodium channel subunits in a mouse model of Dravet syndrome
- Creators
- Ania K Dabrowski - Children's Hospital of PhiladelphiaAla Somarowthu - Children's Hospital of PhiladelphiaSophie R Liebergall - University of PennsylvaniaDamaris N Lorenzo - University of PennsylvaniaEthan M Goldberg - Children's Hospital of Philadelphia
- Resource Type
- Journal article
- Publication Details
- Epilepsia (Copenhagen), Vol.67(8), pp.e133-e140
- DOI
- 10.1002/epi.70336
- PMID
- 42257687
- PMCID
- PMC13525587
- NLM abbreviation
- Epilepsia
- ISSN
- 1528-1167
- eISSN
- 1528-1167
- Publisher
- Wiley
- Grant note
- R01NS110869 / NINDS NIH HHS R01MH127848 / NIMH NIH HHS R01NS137604 / NINDS NIH HHS R01NS110810 / NINDS NIH HHS R01MH136674 / NIMH NIH HHS F31NS132519 / NINDS NIH HHS
- Language
- English
- Electronic publication date
- 06/08/2026
- Academic Unit
- Stead Family Department of Pediatrics; Neurology (Pediatrics)
- Record Identifier
- 9985174710702771
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