[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-1-en-105":3,"doc-seo-162082-105":53,"doc-detail-162082-en":126},{"code":4,"msg":5,"data":6},0,"success",[7,14,19,24,29,34,39,44,49],{"id":8,"doc_module":9,"doc_module_name":10,"category_name":11,"show_sort_weight":12,"slug":13},11,1,"Template","Presentations",90,"presentations",{"id":15,"doc_module":9,"doc_module_name":10,"category_name":16,"show_sort_weight":17,"slug":18},12,"Resumes",80,"resumes",{"id":20,"doc_module":9,"doc_module_name":10,"category_name":21,"show_sort_weight":22,"slug":23},14,"Invoices",70,"invoices",{"id":25,"doc_module":9,"doc_module_name":10,"category_name":26,"show_sort_weight":27,"slug":28},15,"Posters",60,"posters",{"id":30,"doc_module":9,"doc_module_name":10,"category_name":31,"show_sort_weight":32,"slug":33},16,"Social Media",50,"social-media",{"id":35,"doc_module":9,"doc_module_name":10,"category_name":36,"show_sort_weight":37,"slug":38},17,"Forms",40,"forms",{"id":40,"doc_module":9,"doc_module_name":10,"category_name":41,"show_sort_weight":42,"slug":43},18,"Letters",30,"letters",{"id":45,"doc_module":9,"doc_module_name":10,"category_name":46,"show_sort_weight":47,"slug":48},21,"Paper Templates",5,"papers-templates",{"id":50,"doc_module":9,"doc_module_name":10,"category_name":51,"show_sort_weight":4,"slug":52},158,"General","general-158",{"code":4,"msg":54,"data":55},"ok",{"site_id":56,"language":57,"slug":58,"title":59,"keywords":60,"description":61,"schema_data":62,"social_meta":119,"head_meta":121,"extra_data":123,"updated_unix":125},105,"en","understanding-epilepsy-and-sudep-in-mouse-models-with-the-atp1a3-d801n-mutation-based-on-2024-hunanyan-mikati","Understanding Epilepsy and SUDEP in Mouse Models with the ATP1A3 D801N Mutation - Based on 2024 Hunanyan-Mikati","","The study examines epilepsy and sudden unexpected death in epilepsy (SUDEP) in Atp1a3Mashl/+ mice carrying the ATP1A3 D801N mutation, a leading cause of alternating hemiplegia of childhood. ATP1A3 encodes the Na+/K+-ATPase alpha-3 subunit, linking impaired neuronal excitability and brain homeostasis to seizure susceptibility, progressive cardiorespiratory dysregulation, and SUDEP risk. Using EEG/ECG/respiration telemetry, plethysmography, nerve recordings, and histomolecular analyses, the work shows SUDEP occurs during generalized tonic-clonic seizures preceded by apnea, followed by fatal cardiac arrhythmias.",{"@graph":63,"@context":118},[64,80,101],{"@type":65,"itemListElement":66},"BreadcrumbList",[67,71,74,77],{"item":68,"name":69,"@type":70,"position":9},"https://docshare.wps.com","Home","ListItem",{"item":72,"name":10,"@type":70,"position":73},"https://docshare.wps.com/template/",2,{"item":75,"name":11,"@type":70,"position":76},"https://docshare.wps.com/template/presentations/",3,{"item":78,"name":59,"@type":70,"position":79},"https://docshare.wps.com/template/understanding-epilepsy-and-sudep-in-mouse-models-with-the-atp1a3-d801n-mutation-based-on-2024-hunanyan-mikati/162082/",4,{"url":78,"name":59,"@type":81,"image":82,"author":87,"headline":59,"publisher":90,"fileFormat":93,"inLanguage":57,"description":61,"dateModified":94,"datePublished":95,"encodingFormat":93,"isAccessibleForFree":96,"interactionStatistic":97},"DigitalDocument",{"url":83,"@type":84,"width":85,"height":86},"https://docshare.wps.com/thumbnails/understanding-epilepsy-and-sudep-in-mouse-models-with-the-atp1a3-d801n-mutation-based-on-2024-hunanyan-mikati/162082.png","ImageObject",442,249,{"name":88,"@type":89},"Hazel","Person",{"url":68,"name":91,"@type":92},"DocShare","Organization","application/vnd.openxmlformats-officedocument.wordprocessingml.document","2026-09-19","2026-08-30",true,{"@type":98,"interactionType":99,"userInteractionCount":76},"InteractionCounter",{"@type":100},"ViewAction",{"@type":102,"mainEntity":103},"FAQPage",[104,110,114],{"name":105,"@type":106,"acceptedAnswer":107},"Where and when does SUDEP occur in the Atp1a3Mashl/+ mouse model?","Question",{"text":108,"@type":109},"All deaths occur during generalized tonic-clonic seizures (Racine stage V). Seizure clustering and worsening precede SUDEP.","Answer",{"name":111,"@type":106,"acceptedAnswer":112},"What event sequence leads to SUDEP according to the study?",{"text":113,"@type":109},"Apnea is the primary preceding event, followed by severe cardiac arrhythmias that progress to asystole.",{"name":115,"@type":106,"acceptedAnswer":116},"How does ATP1A3 dysfunction contribute to respiratory deficits relevant to SUDEP?",{"text":117,"@type":109},"Baseline apnea susceptibility and abnormal responses to hypoxia/hypercapnia are present. Hypoglossal nerve recordings show reduced respiratory drive, and early breathing irregularities predict fatal respiratory depression.","https://schema.org",{"og:url":78,"og:type":120,"og:title":59,"og:site_name":91,"og:description":61},"article",{"robots":122,"canonical":78},"index,follow",{"doc_id":124,"site_id":56},162082,1788118057,{"code":4,"msg":5,"data":127},{"doc_id":124,"user_id":128,"nickname":88,"user_avatar":129,"doc_module":9,"category_id":8,"category_name":11,"doc_title":59,"doc_description":61,"doc_content":130,"file_id":131,"file_url":132,"file_type":133,"file_size":134,"view_count":76,"is_deleted":4,"is_public":9,"is_downloadable":9,"audit_status":9,"page_count":76,"language":135,"language_code":57,"site_id":56,"html_lang":57,"table_of_contents":136,"faqs":137,"seo_title":138,"seo_description":61,"update_tm":125,"read_time":9},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","Understanding Epilepsy and SUDEP in Mouse Models with the ATP1A3 D801N Mutation\nBackground and Relevance to Epilepsy Research\nThe study investigates epilepsy and sudden unexpected death in epilepsy (SUDEP) in the Atp1a3Mashl/+ mouse model, which carries the D801N mutation in ATP1A3—the most common human mutation linked to Alternating Hemiplegia of Childhood (AHC). ATP1A3 encodes the alpha-3 subunit of Na+/K+-ATPase, an enzyme critical for neuronal excitability and brain homeostasis. This study provides essential insights into how ATPase dysfunction contributes to seizure susceptibility, central cardiorespiratory dysregulation, and increased risk of SUDEP.\nGiven that many epilepsy models manifest secondary ATPase dysfunction, this research suggests that ATP1A3-related mechanisms might be broadly relevant to SUDEP pathophysiology in other forms of epilepsy.\nKey Research Objectives\nCharacterize the relationship between seizures and SUDEP in Atp1a3Mashl/+ mice.\nDetermine whether SUDEP is due to terminal apnea, lethal cardiac arrhythmias, or a combination of both.\nInvestigate baseline and progressive cardiorespiratory abnormalities in these mice.\nIdentify potential therapeutic targets for preventing SUDEP in ATP1A3-related epilepsies.\nMethodology\nTo study these hypotheses, the researchers performed:\nVideo-telemetry recordings (EEG, ECG, respiration) in awake, freely moving mice to correlate seizure activity with SUDEP.\nWhole-body plethysmography to assess breathing function and apnea susceptibility.\nHypoglossal nerve recordings to evaluate central respiratory drive responses.\nHistopathological and molecular analyses to explore structural and functional changes in brainstem circuits.\nFindings and Scientific Implications\n1. SUDEP Always Occurred During Seizures\nAll deaths occurred during generalized tonic-clonic seizures (Racine stage V).\nPreterminal seizures were less severe than terminal seizures, indicating progressive seizure exacerbation.\nSeizure clustering preceded SUDEP, suggesting a worsening epileptogenic state leading to fatal events.\n2. Cardiorespiratory Dysfunction Preceded SUDEP\nBradycardia and bradypnea began before seizures and worsened during ictal periods.\nApnea was the primary event preceding SUDEP, followed by severe cardiac arrhythmias leading to asystole.\nSinus pauses and AV blocks increased progressively before death, indicating progressive cardiac instability.\n3. ATP1A3 Dysfunction Leads to Central Respiratory Deficits\nWhole-body plethysmography showed a baseline predisposition to apnea, with abnormal responses to hypoxia/hypercapnia.\nHypoglossal nerve recordings demonstrated reduced respiratory drive, independent of peripheral vagal input.\nBreathing irregularities (high CV of BR) were detected early, predicting susceptibility to fatal respiratory depression.\n4. Parallels with Human AHC and SUDEP Mechanisms\nAHC patients with ATP1A3 mutations exhibit severe epileptic encephalopathy, sleep-related apneas, and cardiac arrhythmias.\nSimilar findings in humans suggest ATPase dysfunction as a critical factor in SUDEP risk across different epilepsy syndromes.\nThese results strengthen the model's translational value, supporting its use in drug testing for SUDEP prevention.\nPotential Mechanisms of SUDEP in ATP1A3-Related Epilepsy\nCortical spreading depolarization (SD) spreading to the brainstem\nATP1A3 mutations predispose neurons to SD, which may cause catastrophic cardiorespiratory failure.\nProgressive brainstem dysfunction due to recurrent seizures\nRepeated hypoxic insults exacerbate neuronal loss in cardiorespiratory nuclei, leading to terminal dysfunction.\nIntrinsic ATPase dysfunction causing cardiorespiratory instability\nLoss of ATPase activity affects brainstem autonomic centers, disrupting cardiac and respiratory rhythmicity.\nFailure of seizure-induced compensatory mechanisms\nUnlike Dravet syndrome (SCN1A mutations), ATP1A3-related SUDEP appears primarily respiratory-driven, with arrhythmias as a secondary factor.","cbCair29CbtETPJV","https://ap.wps.com/l/cbCair29CbtETPJV","docx",19125,"English","# Background and Relevance to Epilepsy Research\n## Key Research Objectives\n## Methodology\n# Findings and Scientific Implications\n## SUDEP Occurs During Seizures\n## Cardiorespiratory Dysfunction Before SUDEP\n## ATP1A3 Dysfunction and Respiratory Deficits\n## Parallels with Human AHC and SUDEP\n# Potential Mechanisms and Implications\n## Mechanisms of SUDEP in ATP1A3-Related Epilepsy\n## Clinical and Translational Implications\n## Future Research Directions\n# Conclusion","[{\"question\":\"Where and when does SUDEP occur in the Atp1a3Mashl/+ mouse model?\",\"answer\":\"All deaths occur during generalized tonic-clonic seizures (Racine stage V). Seizure clustering and worsening precede SUDEP.\"},{\"question\":\"What event sequence leads to SUDEP according to the study?\",\"answer\":\"Apnea is the primary preceding event, followed by severe cardiac arrhythmias that progress to asystole.\"},{\"question\":\"How does ATP1A3 dysfunction contribute to respiratory deficits relevant to SUDEP?\",\"answer\":\"Baseline apnea susceptibility and abnormal responses to hypoxia/hypercapnia are present. Hypoglossal nerve recordings show reduced respiratory drive, and early breathing irregularities predict fatal respiratory depression.\"}]","Understanding Epilepsy and SUDEP in Mouse Models with the ATP1A3 D801N Mutation - Based on 2024 Hunanyan-Mikati | DOCX"]