Early-life febrile seizures worsen adult phenotypes in Scn1a mutants.

ABSTRACT: Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Na_v1.1 channel, are responsible for a number of epilepsy disorders including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS). Patients with SCN1A mutations often experience prolonged early-life febrile seizures (FSs), raising the possibility that these events may influence epileptogenesis and lead to more severe adult phenotypes. To test this hypothesis, we subjected 21-23-day-old mice expressing the human SCN1A GEFS+ mutation R1648H to prolonged hyperthermia, and then examined seizure and behavioral phenotypes during adulthood. We found that early-life FSs resulted in lower latencies to induced seizures, increased severity of spontaneous seizures, hyperactivity, and impair

SUBMITTER: Dutton SBB 

PROVIDER: S-EPMC5538963 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature