Authors
Constanza Bravo-Rossainz Baez, Xian Xin, Hang Lyu, Daniil Kirianov, Ying Sun, Erik Späte, Mariapia Grassia, Birgit Engeland, Malte Stockebrand, Konstantin Khodosevich, Ulrike B S Hedrich, Dirk Isbrandt, Friederike Pfeiffer
Published in
Acta neuropathologica communications. Volume 14. Issue 1. Oct 07, 2026. Epub Oct 07, 2026.
Abstract
Gain-of-function variants in SCN2A, encoding the voltage-gated sodium channel NaV1.2, cause developmental and epileptic encephalopathies characterized by seizures, developmental delay, and white matter abnormalities. While NaV1.2 is known to regulate neuronal excitability, its role in oligodendroglial cells is unclear. Here, we show that NaV1.2 is expressed in early oligodendrocyte lineage stages. In mice carrying the gain-of-function Scn2ap.A263V variant, oligodendrocyte precursor cells displayed similar NaV1.2 expression, but altered electrophysiological properties and calcium signaling. Single-cell transcriptomics revealed stage-specific changes in oligodendroglial maturation during early postnatal development, associated with lower variability and slightly faster conduction velocities. In adult mutant mice, gray matter myelination was increased without changes in oligodendrocyte numbers or myelin structure. Since NaV1.2 was absent from mature oligodendrocytes, the enhanced myelination likely reflects an activity-dependent adaptation to altered neuronal network activity rather than a primary myelinopathy. These findings identify a glial contribution to SCN2A-related disease mechanisms and underscore the need to consider neuron-glia interactions when developing targeted therapies for epilepsy.
PMID:
42855710
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.
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