ArticleAnnals of neurology2013
Dravet syndrome patient-derived neurons suggest a novel epilepsy mechanism.
Article in Annals of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 244 citations in OpenAlex.
- GABACellular and molecular neurobiology · 2026Review
- Urine-Derived iPSC Neurospheres Uncover Proteomic Correlates of Clinical Severity in Dravet Syndrome.Journal of neurochemistry · 2026Article
- Ameliorating Seizures in Dravet Syndrome: A Review of Newly Approved and Investigational Drugs, RNA and Gene-Based Therapies.CNS drugs · 2026Review
- Dravet Syndrome Patient-Derived Neural Cells Present Altered Levels of Potassium, Copper, and Zinc.ACS chemical neuroscience · 2026Article
- Ectopic sodium channel expression decreases excitability of Drosophila Kenyon cells.The Journal of physiology · 2025Article
- Depolarization block induction via slow NaScientific reports · 2025Article
- Ion channels and G protein-coupled receptors: Cannabidiol actions on disorders of excitability and synaptic excitatory-inhibitory ratio.Molecular pharmacology · 2025Review
- Genotype-function-phenotype correlations for SCN1A variants identified by clinical genetic testing.Annals of clinical and translational neurology · 2025Article
- An integrated in vitro human iPSCs-derived neuron and in vivo animal approach for preclinical screening of anti-seizure compounds.Journal of advanced research · 2024Article
- Epigenetic insights into GABAergic development in Dravet Syndrome iPSC and therapeutic implications.eLife · 2024Article
- In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.Stem cell reports · 2024Review
- In vitro human cell culture models in a bench-to-bedside approach to epilepsy.Epilepsia open · 2024Review
- Targeted blockade of aberrant sodium current in a stem cell-derived neuron model of SCN3A encephalopathy.Brain : a journal of neurology · 2024Article
- Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Integrative analysis of epilepsy-associated genes reveals expression-phenotype correlations.Scientific reports · 2024Article
- Advances in physiological and clinical relevance of hiPSC-derived brain models for precision medicine pipelines.Frontiers in cellular neuroscience · 2024Review
- Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model.Brain communications · 2024Article
- SCN1A-deficient excitatory neuronal networks display mutation-specific phenotypes.Brain : a journal of neurology · 2023Article
- Testing of putative antiseizure drugs in a preclinical Dravet syndrome zebrafish model.bioRxiv : the preprint server for biology · 2023Article
- Dysfunctional sodium channel kinetics as a novel epilepsy mechanism in chromosome 15q11-q13 duplication syndrome.Epilepsia · 2023Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum.2015
Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
objectiveNeuronal channelopathies cause brain disorders, including epilepsy, migraine, and ataxia. Despite the development of mouse models, pathophysiological mechanisms for these disorders remain uncertain. One particularly devastating channelopathy is Dravet syndrome (DS), a severe childhood epilepsy typically caused by de novo dominant mutations in the SCN1A gene encoding the voltage-gated sodium channel Na(v) 1.1. Heterologous expression of mutant channels suggests loss of function, raising the quandary of how loss of sodium channels underlying action potentials produces hyperexcitability. Mouse model studies suggest that decreased Na(v) 1.1 function in interneurons causes disinhibition. We aim to determine how mutant SCN1A affects human neurons using the induced pluripotent stem cell (iPSC) method to generate patient-specific neurons.
methodsHere we derive forebrain-like pyramidal- and bipolar-shaped neurons from 2 DS subjects and 3 human controls by iPSC reprogramming of fibroblasts. DS and control iPSC-derived neurons are compared using whole-cell patch clamp recordings. Sodium current density and intrinsic neuronal excitability are examined.
resultsNeural progenitors from DS and human control iPSCs display a forebrain identity and differentiate into bipolar- and pyramidal-shaped neurons. DS patient-derived neurons show increased sodium currents in both bipolar- and pyramidal-shaped neurons. Consistent with increased sodium currents, both types of patient-derived neurons show spontaneous bursting and other evidence of hyperexcitability. Sodium channel transcripts are not elevated, consistent with a post-translational mechanism.
interpretationThese data demonstrate that epilepsy patient-specific iPSC-derived neurons are useful for modeling epileptic-like hyperactivity. Our findings reveal a previously unrecognized cell-autonomous epilepsy mechanism potentially underlying DS, and offer a platform for screening new antiepileptic therapies.
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Registered trials
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.