{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:55:44Z","timestamp":1772067344086,"version":"3.50.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["UO1 NS090415"],"award-info":[{"award-number":["UO1 NS090415"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["P30AG066512"],"award-info":[{"award-number":["P30AG066512"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005481","name":"New York University School of Medicine","doi-asserted-by":"crossref","award":["P01AG060882"],"award-info":[{"award-number":["P01AG060882"]}],"id":[{"id":"10.13039\/100005481","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Brainstem nuclei dysfunction is implicated in sudden unexpected death in epilepsy. In animal models, deficient serotonergic activity is associated with seizure-induced respiratory arrest. In humans, glia are decreased in the ventrolateral medullary pre-Botzinger complex that modulate respiratory rhythm, as well as in the medial medullary raphe that modulate respiration and arousal. Finally, sudden unexpected death in epilepsy cases have decreased midbrain volume. To understand the potential role of brainstem nuclei in sudden unexpected death in epilepsy, we evaluated molecular signalling pathways using localized proteomics in microdissected midbrain dorsal raphe and medial medullary raphe serotonergic nuclei, as well as the ventrolateral medulla in brain tissue from epilepsy patients who died of sudden unexpected death in epilepsy and other causes in diverse epilepsy syndromes and non-epilepsy control cases (n\u2009=\u200915\u201316 cases per group\/region). Compared with the dorsal raphe of non-epilepsy controls, we identified 89 proteins in non-sudden unexpected death in epilepsy and 219 proteins in sudden unexpected death in epilepsy that were differentially expressed. These proteins were associated with inhibition of EIF2 signalling (P-value of overlap\u2009=\u20091.29\u2009\u00d7\u200910\u22128, z\u2009=\u2009\u22122.00) in non-sudden unexpected death in epilepsy. In sudden unexpected death in epilepsy, there were 10 activated pathways (top pathway: gluconeogenesis I, P-value of overlap\u2009=\u20093.02\u2009\u00d7\u200910\u22126, z\u2009=\u20092.24) and 1 inhibited pathway (fatty acid beta-oxidation, P-value of overlap\u2009=\u20092.69\u2009\u00d7\u200910\u22124, z\u2009=\u2009\u22122.00). Comparing sudden unexpected death in epilepsy and non-sudden unexpected death in epilepsy, 10 proteins were differentially expressed, but there were no associated signalling pathways. In both medullary regions, few proteins showed significant differences in pairwise comparisons. We identified altered proteins in the raphe and ventrolateral medulla of epilepsy patients, including some differentially expressed in sudden unexpected death in epilepsy cases. Altered signalling pathways in the dorsal raphe of sudden unexpected death in epilepsy indicate a shift in cellular energy production and activation of G-protein signalling, inflammatory response, stress response and neuronal migration\/outgrowth. Future studies should assess the brain proteome in relation to additional clinical variables (e.g. recent tonic\u2013clonic seizures) and in more of the reciprocally connected cortical and subcortical regions to better understand the pathophysiology of epilepsy and sudden unexpected death in epilepsy.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac186","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T18:45:34Z","timestamp":1657651534000},"source":"Crossref","is-referenced-by-count":15,"title":["Raphe and ventrolateral medulla proteomics in epilepsy and sudden unexpected death in epilepsy"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1371-9861","authenticated-orcid":false,"given":"Dominique F","family":"Leitner","sequence":"first","affiliation":[{"name":"Comprehensive Epilepsy Center, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny","family":"Kanshin","sequence":"additional","affiliation":[{"name":"Proteomics Laboratory, Division of Advanced Research Technologies, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manor","family":"Askenazi","sequence":"additional","affiliation":[{"name":"Biomedical Hosting LLC , Arlington, MA 02140 , USA"},{"name":"Department of Biochemistry and Molecular Pharmacology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arline","family":"Faustin","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neurology, Department of Neurology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"},{"name":"Department of Pathology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1068-1797","authenticated-orcid":false,"given":"Daniel","family":"Friedman","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sasha","family":"Devore","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrix","family":"Ueberheide","sequence":"additional","affiliation":[{"name":"Proteomics Laboratory, Division of Advanced Research Technologies, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"},{"name":"Department of Biochemistry and Molecular Pharmacology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"},{"name":"Center for Cognitive Neurology, Department of Neurology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3379-8966","authenticated-orcid":false,"given":"Thomas","family":"Wisniewski","sequence":"additional","affiliation":[{"name":"Center for Cognitive Neurology, Department of Neurology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"},{"name":"Department of Pathology, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"},{"name":"Department of Psychiatry, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center, Grossman School of Medicine, New York University , 223 East 34th Street, New York, NY 10016 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"issue":"10","key":"2022072108590329900_fcac186-B1","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/S1474-4422(16)30158-2","article-title":"Sudden unexpected death in epilepsy: Epidemiology, mechanisms, and prevention","volume":"15","author":"Devinsky","year":"2016","journal-title":"Lancet Neurol."},{"issue":"10","key":"2022072108590329900_fcac186-B2","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/S1474-4422(13)70214-X","article-title":"Incidence and mechanisms of 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