Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
25 05 2021
25 05 2021
Historique:
received:
11
08
2020
accepted:
26
02
2021
pubmed:
30
4
2021
medline:
29
6
2021
entrez:
29
4
2021
Statut:
ppublish
Résumé
To identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to control patients with epilepsy. For proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected postmortem brain tissue of 12 patients with SUDEP and 14 with non-SUDEP epilepsy. For transcriptomics analyses, we evaluated hippocampus and temporal cortex surgical brain tissue from patients with mesial temporal lobe epilepsy: 6 low-risk and 8 high-risk SUDEP as determined by a short (<50 seconds) or prolonged (≥50 seconds) postictal generalized EEG suppression (PGES) that may indicate severely depressed brain activity impairing respiration, arousal, and protective reflexes. In autopsy hippocampus and cortex, we observed no proteomic differences between patients with SUDEP and those with non-SUDEP epilepsy, contrasting with our previously reported robust differences between epilepsy and controls without epilepsy. Transcriptomics in hippocampus and cortex from patients with surgical epilepsy segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 long noncoding RNAs, 3 pending) in hippocampus. The SUDEP proteome and high-risk SUDEP transcriptome were similar to those in other patients with epilepsy in hippocampus and cortex, consistent with diverse epilepsy syndromes and comorbid conditions associated with SUDEP. Studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions, may identify molecular mechanisms of SUDEP.
Identifiants
pubmed: 33910938
pii: WNL.0000000000011999
doi: 10.1212/WNL.0000000000011999
pmc: PMC8205452
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2639-e2652Subventions
Organisme : NIA NIH HHS
ID : P30 AG066512
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058267
Pays : United States
Organisme : NIH HHS
ID : S10 OD010582
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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