ArticleAnnals of neurology2023
Sudden Unexpected Death in Epilepsy and Respiratory Defects in a Mouse Model of DEPDC5-Related Epilepsy.
Article in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- A Change of Heart forEpilepsy currents · 2026Article
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- SUDEP update 2026: recent advances in experimental and clinical research.Current opinion in neurology · 2026Review
- Translational Research Symposium: Current State of SUDEP Research.Epilepsy currents · 2026Article
- Early death and neuronal abnormalities inbioRxiv : the preprint server for biology · 2025Article
- Altered PI3K/mTOR Signaling within the Forebrain Leads to Respiratory Deficits in a Mouse Model of Epilepsy.eNeuro · 2025Article
- Peri-ictal respiratory dysfunction: Expanding the association between mTOR pathway disorders and ictal central apnea.Epilepsia · 2025Article
- Article
- Neuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors.Neurobiology of disease · 2025Article
- Seizures and premature death in mice with targeted Kv1.1 deficiency in corticolimbic circuits.Brain communications · 2025Article
- Refinement of the pilocarpine-induced status epilepticus model in mice to improve mortality outcomes.Frontiers in neuroscience · 2025Article
- Ictal and Postictal Central Apnea inNeurology. Genetics · 2024Article
- Beyond the seizure: unveiling the mechanism of death in SUDEP through integrated scene and autopsy analysis.Frontiers in neurologyArticle
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesDEPDC5 is a common causative gene in familial focal epilepsy with or without malformations of cortical development. Its pathogenic variants also confer a significantly higher risk for sudden unexpected death in epilepsy (SUDEP), providing opportunities to investigate the pathophysiology intersecting neurodevelopment, epilepsy, and cardiorespiratory function. There is an urgent need to gain a mechanistic understanding of DEPDC5-related epilepsy and SUDEP, identify biomarkers for patients at high risk, and develop preventive interventions.
methodsDepdc5 was specifically deleted in excitatory or inhibitory neurons in the mouse brain to determine neuronal subtypes that drive epileptogenesis and SUDEP. Electroencephalogram (EEG), cardiac, and respiratory recordings were performed to determine cardiorespiratory phenotypes associated with SUDEP. Baseline respiratory function and the response to hypoxia challenge were also studied in these mice.
resultsDepdc5 deletion in excitatory neurons in cortical layer 5 and dentate gyrus caused frequent generalized tonic-clonic seizures and SUDEP in young adult mice, but Depdc5 deletion in cortical interneurons did not. EEG suppression immediately following ictal offset was observed in fatal and non-fatal seizures, but low amplitude rhythmic theta frequency activity was lost only in fatal seizures. In addition, these mice developed baseline respiratory dysfunction prior to SUDEP, during which ictal apnea occurred long before terminal cardiac asystole.
interpretationDepdc5 deletion in excitatory neurons is sufficient to cause DEPDC5-related epilepsy and SUDEP. Ictal apnea and respiratory dysregulation play critical roles in SUDEP. Our study also provides a novel mouse model to investigate the underlying mechanisms of DEPDC5-related epilepsy and SUDEP. ANN NEUROL 2023;94:812-824.
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