ArticleNeurobiology of disease2014
Role of the hippocampus in Nav1.6 (Scn8a) mediated seizure resistance.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Voltage-gated sodium channels in the nervous system: Molecular physiology to therapeutic interventions.Neural regeneration research · 2026Article
- A research roadmap for SCN8A-related disorders: addressing knowledge gaps and aligning research priorities across stakeholders.Orphanet journal of rare diseases · 2025Article
- Classification of Current Experimental Models of Epilepsy.Brain sciences · 2024Review
- Exosomal TNF-α mediates voltage-gated Na+ channel 1.6 overexpression and contributes to brain tumor-induced neuronal hyperexcitability.The Journal of clinical investigation · 2024Article
- Long-Term Downregulation of the Sodium Channel Gene Scn8a Is Therapeutic in Mouse Models of SCN8A Epilepsy.Annals of neurology · 2024Article
- Relationship between right-to-left shunt, hypoxia, and epilepsy.Epilepsia open · 2023Observational
- Removal of KCNQ2 from parvalbumin-expressing interneurons improves anti-seizure efficacy of retigabine.Experimental neurology · 2022Article
- Article
- Autistic-like behavior, spontaneous seizures, and increased neuronal excitability in a Scn8a mouse model.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Review
- Sodium channelopathies in neurodevelopmental disorders.Nature reviews. Neuroscience · 2021Review
- Pathogenic in-Frame Variants inFrontiers in pharmacology · 2021Article
- Dendritic Integration Dysfunction in Neurodevelopmental Disorders.Developmental neuroscience · 2021Review
- Comparison of the toxicokinetics of the convulsants picrotoxinin and tetramethylenedisulfotetramine (TETS) in mice.Archives of toxicology · 2020Article
- PRRT2 frameshift mutation reduces its mRNA stability resulting loss of function in paroxysmal kinesigenic dyskinesia.Biochemical and biophysical research communications · 2020Article
- Distinct functional alterations in SCN8A epilepsy mutant channels.The Journal of physiology · 2020Article
- Prominent role of forebrain excitatory neurons in SCN8A encephalopathy.Brain : a journal of neurology · 2019Article
- Differential roles of NaScientific reports · 2018Article
- Selective targeting of Scn8a prevents seizure development in a mouse model of mesial temporal lobe epilepsy.Scientific reports · 2018Article
- The NaFrontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
SCN1A mutations are the main cause of the epilepsy disorders Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+). Mutations that reduce the activity of the mouse Scn8a gene, in contrast, are found to confer seizure resistance and extend the lifespan of mouse models of DS and GEFS+. To investigate the mechanism by which reduced Scn8a expression confers seizure resistance, we induced interictal-like burst discharges in hippocampal slices of heterozygous Scn8a null mice (Scn8a(med/+)) with elevated extracellular potassium. Scn8a(med/+) mutants exhibited reduced epileptiform burst discharge activity after P20, indicating an age-dependent increased threshold for induction of epileptiform discharges. Scn8a deficiency also reduced the occurrence of burst discharges in a GEFS+ mouse model (Scn1a(R1648H/+)). There was no detectable change in the expression levels of Scn1a (Nav1.1) or Scn2a (Nav1.2) in the hippocampus of adult Scn8a(med/+) mutants. To determine whether the increased seizure resistance associated with reduced Scn8a expression was due to alterations that occurred during development, we examined the effect of deleting Scn8a in adult mice. Global Cre-mediated deletion of a heterozygous floxed Scn8a allele in adult mice was found to increase thresholds to chemically and electrically induced seizures. Finally, knockdown of Scn8a gene expression in the adult hippocampus via lentiviral Cre injection resulted in a reduction in the number of EEG-confirmed seizures following the administration of picrotoxin. Our results identify the hippocampus as an important structure in the mediation of Scn8a-dependent seizure protection and suggest that selective targeting of Scn8a activity might be efficacious in patients with epilepsy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.