{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:28:18Z","timestamp":1786976898336,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AT011652"],"award-info":[{"award-number":["R01 AT011652"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL156989"],"award-info":[{"award-number":["R01 HL156989"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS113824"],"award-info":[{"award-number":["R01 NS113824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS117170"],"award-info":[{"award-number":["U54NS117170"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      <jats:italic>DEPDC5<\/jats:italic>\n                      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\u2010related epilepsy and SUDEP, identify biomarkers for patients at high risk, and develop preventive interventions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Depdc5<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Depdc5<\/jats:italic>\n                      deletion in excitatory neurons in cortical layer 5 and dentate gyrus caused frequent generalized tonic\u2013clonic seizures and SUDEP in young adult mice, but\n                      <jats:italic>Depdc5<\/jats:italic>\n                      deletion in cortical interneurons did not. EEG suppression immediately following ictal offset was observed in fatal and non\u2010fatal 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Depdc5<\/jats:italic>\n                      deletion in excitatory neurons is sufficient to cause\n                      <jats:italic>DEPDC5<\/jats:italic>\n                      \u2010related 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\u2010related epilepsy and SUDEP. ANN NEUROL 2023;94:812\u2013824\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26773","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T06:59:54Z","timestamp":1692687594000},"page":"812-824","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sudden Unexpected Death in Epilepsy and Respiratory Defects in a Mouse Model of\n                    <scp>DEPDC5<\/scp>\n                    \u2010Related Epilepsy"],"prefix":"10.1002","volume":"94","author":[{"given":"Hsin\u2010Yi","family":"Kao","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Yao","sequence":"additional","affiliation":[{"name":"Life Sciences Institute University of Michigan  Ann Arbor MI"},{"name":"Department of Neurosurgery Shengjing Hospital of 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