Leitner, DF;
Mills, JD;
Pires, G;
Faustin, A;
Drummond, E;
Kanshin, E;
Nayak, S;
... Devinsky, O; + view all
(2021)
Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients.
Neurology
10.1212/WNL.0000000000011999.
(In press).
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Abstract
OBJECTIVE: To identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to epilepsy control patients. METHODS: For proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected post-mortem brain tissue of 12 SUDEP and 14 non-SUDEP epilepsy patients. For transcriptomics analyses, we evaluated hippocampus and temporal cortex surgical brain tissue from mesial temporal lobe epilepsy (MTLE) patients: 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. RESULTS: In autopsy hippocampus and cortex, we observed no proteomic differences between SUDEP and non-SUDEP epilepsy patients, contrasting with our previously reported robust differences between epilepsy and non-epilepsy control patients. Transcriptomics in hippocampus and cortex from surgical epilepsy patients segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 lncRNAs, three pending) in hippocampus. CONCLUSION: The SUDEP proteome and high-risk SUDEP transcriptome were similar to other epilepsy patients in hippocampus and frontal cortex, consistent with diverse epilepsy syndromes and comorbidities associated with SUDEP. Studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions may identify molecular mechanisms of SUDEP.
| Type: | Article |
|---|---|
| Title: | Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/WNL.0000000000011999 |
| Publisher version: | https://doi.org/10.1212/WNL.0000000000011999 |
| Language: | English |
| Additional information: | © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10127329 |
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