Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients.
Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients.
复制标题
DOI：
10.1212/wnl.0000000000011999
复制
发表时间：
2021-05-25
期刊：
影响因子：
9.9
通讯作者：
Devinsky O
中科院分区：
文献类型：
--
作者：
Leitner DF;Mills JD;Pires G;Faustin A;Drummond E;Kanshin E;Nayak S;Askenazi M;Verducci C;Chen BJ;Janitz M;Anink JJ;Baayen JC;Idema S;van Vliet EA;Devore S;Friedman D;Diehl B;Scott C;Thijs R;Wisniewski T;Ueberheide B;Thom M;Aronica E;Devinsky O
与对照癫痫患者相比，确定癫痫猝死（SUDEP）和高风险SUDEP的分子信号通路。对于蛋白质组学分析，我们评估了12例SUDEP患者和14例非SUDEP癫痫患者死后脑组织的海马和额叶皮质。对于转录组学分析，我们评估了内侧颞叶癫痫患者的海马和颞叶皮质手术脑组织：6例低风险和8例高风险SUDEP，由短（<50秒）或长（≥50秒）的发作后全身性EEG抑制（PGES）确定，这可能表明严重抑制的脑活动损害呼吸，觉醒和保护性反射。在尸检海马和皮质中，我们观察到SUDEP患者和非SUDEP癫痫患者之间没有蛋白质组差异，与我们先前报道的癫痫和无癫痫对照之间的显著差异形成对比。通过PGES分离的手术癫痫患者的海马和皮质中的转录组学鉴定了海马中的55个差异表达基因（37个蛋白质编码，15个长非编码RNA，3个待决）。SUDEP蛋白质组和高风险SUDEP转录组与海马和皮质中的其他癫痫患者相似，与多种癫痫综合征和与SUDEP相关的共病状况一致。对更大队列和不同癫痫综合征以及其他解剖区域的研究可能会确定SUDEP的分子机制。
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.