| First Author | Vermudez SAD | Year | 2025 |
| Journal | Neuroreport | Volume | 36 |
| Issue | 8 | Pages | 383-388 |
| PubMed ID | 40203292 | Mgi Jnum | J:369828 |
| Mgi Id | MGI:8221821 | Doi | 10.1097/WNR.0000000000002159 |
| Citation | Vermudez SAD, et al. (2025) Sex differences in seizure presentation in a Dravet syndrome mouse model. Neuroreport 36(8):383-388 |
| abstractText | OBJECTIVES: Dravet syndrome is an epileptic encephalopathy mostly because of haploinsufficiency of the SCN1A voltage-gated sodium channel subunit. Disease presentation (i.e. severe seizures and early life mortality) is faithfully modeled in mice haploinsufficient in Scn1a ( Scn1a+/ - ). However, the characterization of sex differences in mortality and seizure morbidity is limited. Given the reliance of mouse models for studying disease pathophysiology and for the development of novel treatments, we tested whether disease presentation differed in juvenile and adult female and male Scn1a+/ - mice. METHODS: Mortality and seizure morbidity were quantified in juvenile and adult female and male Scn1a+/ - animals on an F1 hybrid C57 x 129S6 background. RESULTS: Mortality was significantly higher in female Scn1a+/ - mice compared with males regardless of age, and juvenile female Scn1a+/ - mice had a significantly lower febrile seizure threshold than age-matched Scn1a+/ - males. Conversely, long-term video EEG recordings revealed that adult male Scn1a+/ - mice had significantly more frequent and longer spontaneous seizures than adult females. Adult female Scn1a+/- mice, however, were significantly more hyperactive, which may indicate sleep impairment. CONCLUSION: The phenotypic presentation of Scn1a+/ - mice is sex-dependent which may have translational implications for understanding basic pathophysiological mechanisms as well as therapeutic drug discovery in Dravet syndrome. |
