Early-life febrile seizures worsen adult phenotypes in Scn1a mutants
| Autor: | Ligia A. Papale, Karoni Dutt, Sandra L. Helmers, Alan L. Goldin, Stacey B. B. Dutton, Andrew Escayg |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male GEFS Action Potentials Convulsants Neurodegenerative Inbred C57BL Bioinformatics medicine.disease_cause Epileptogenesis Hippocampus Transgenic Febrile Epilepsy Mice 0302 clinical medicine Flurothyl Psychology 2.1 Biological and endogenous factors SCN1A Aetiology Pediatric Mutation Age Factors Phenotype Neurology Anesthesia Neurological Disease Progression Female GEFS+ Hyperthermia Febrile seizures Clinical Sciences Na(v)1.1 Mice Transgenic Arginine Article Seizures Febrile 03 medical and health sciences Slice preparation Developmental Neuroscience Dravet syndrome Seizures Genetics medicine Reaction Time Animals Humans Histidine Neurology & Neurosurgery Animal business.industry Sodium channel Induced Neurosciences Recognition Psychology Hyperthermia Induced Newborn medicine.disease Brain Disorders Mice Inbred C57BL NAV1.1 Voltage-Gated Sodium Channel Recognition Disease Models Animal 030104 developmental biology Animals Newborn Disease Models Exploratory Behavior business 030217 neurology & neurosurgery |
| Zdroj: | Dutton, SBB; Dutt, K; Papale, LA; Helmers, S; Goldin, AL; & Escayg, A. (2017). Early-life febrile seizures worsen adult phenotypes in Scn1a mutants. EXPERIMENTAL NEUROLOGY, 293, 159-171. doi: 10.1016/j.expneurol.2017.03.026. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/2d6880qf |
| Popis: | Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Nav1.1 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 impairments in social behavior and recognition memory during adulthood. Biophysical analysis of brain slice preparations revealed an increase in epileptiform activity in CA3 pyramidal neurons along with increased action potential firing, providing a mechanistic basis for the observed worsening of adult phenotypes. These findings demonstrate the long-term negative impact of early-life FSs on disease outcomes. This has important implications for the clinical management of this patient population and highlights the need for therapeutic interventions that could ameliorate disease progression. |
| Databáze: | OpenAIRE |
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