Defects of Oligodendrocyte Migration in the Scn1b−/− Mouse Model of Dravet Syndrome

Abstract

The Scn1b−/− mouse is a model of Dravet Syndrome (DS), a severe pediatric and developmental epileptic encephalopathy that begins in the first year of life and has multiple comorbidities. Scn1b−/− mice have severe seizures beginning at postnatal day (P)10 and die prior to ~P21. DS patients display defects in white matter, which may contribute to cognitive impairment, language issues, and problems with movement. Our previous research demonstrated that there are fewer nodes of Ranvier and that neuronal migration is impaired in Scn1b−/− brain. The purpose of this study is to determine if Scn1b−/− oligodendrocytes (OLs) migrate correctly from birth in the ventricles to destinations in the cortex. We chose to look at migration from the ventricles to cortical layers II/III and layers V/VI. We hypothesized that we would observe impairments in OL migration in Scn1b−/− animals compared to wildtype. We tested this hypothesis using Scn1b wildtype and Scn1b−/− mice in which OL lineage cells have been genetically labeled with green fluorescent protein (GFP). We performed immunocytochemistry on brain slices from mice of both genotypes at P13‐14 and P17‐18, using CDP as a marker for cortical layers II/III and CTIP2 as a marker of cortical layers V/VI, and then counting the number of GFP+ cells which had migrated to each of these regions. Our data demonstrate that, although the numbers of OLs in layers V/VI were similar between genotypes at both ages, there were fewer OLs in layers II/III in Scn1b−/− brain, suggesting that OL migration in these mice is impaired.Support or Funding InformationFunded by: R37NS076752 to LLI.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.