Wang Yi-Wei, Wang Liang, Yuan Sheng-Jie, Zhang Yuan, Zhang Xin, Zhou Le-Ting
Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Department of Internal Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Front Aging Neurosci. 2022 Jun 28;14:900350. doi: 10.3389/fnagi.2022.900350. eCollection 2022.
Postoperative cognitive dysfunction (POCD) is a common complication characterized by a significant cognitive decline. Increasing evidence suggests an association between the pathogenesis of POCD and Alzheimer's disease (AD). However, a comprehensive understanding of their relationships is still lacking.
First, related databases were obtained from GEO, ArrayExpress, CNGB, and DDBJ repositories. analysis was performed on the raw data using a uniform bioinformatics workflow. Then, macro- and micro-level comparisons were conducted between the transcriptomic changes associated with AD and POCD. Lastly, POCD was induced in male C57BL/6j mice and the hippocampal expression levels of mRNAs of interest were verified by PCR and compared to those in AD congenic models.
There was a very weak correlation in the fold-changes in protein-coding transcripts between AD and POCD. Overall pathway-level comparison suggested that AD and POCD are two disease entities. Consistently, in the classical AD pathway, the mitochondrial complex and tubulin mRNAs were downregulated in both the POCD hippocampus and cortex. POCD and AD hippocampi might share the same pathways, such as tryptophan metabolism, but undergo different pathological changes in phagosome and transferrin endocytosis pathways. The core cluster in the hippocampal network was mainly enriched in mitosis-related pathways. The hippocampal expression levels of genes of interest detected by PCR showed good consistency with those generated by high throughput platforms.
POCD and AD are associated with different transcriptomic changes despite their similar clinical manifestations. This study provides a valuable resource for identifying biomarkers and therapeutic targets for POCD.
术后认知功能障碍（POCD）是一种以显著认知衰退为特征的常见并发症。越来越多的证据表明POCD的发病机制与阿尔茨海默病（AD）之间存在关联。然而，对它们之间关系的全面理解仍然缺乏。
首先，从基因表达综合数据库（GEO）、ArrayExpress数据库、中国国家基因库（CNGB）和DNA数据库（DDBJ）中获取相关数据库。使用统一的生物信息学工作流程对原始数据进行分析。然后，对与AD和POCD相关的转录组变化进行宏观和微观层面的比较。最后，在雄性C57BL/6j小鼠中诱导POCD，并通过聚合酶链反应（PCR）验证感兴趣的mRNA在海马体中的表达水平，并与AD同源模型中的表达水平进行比较。
AD和POCD之间蛋白质编码转录本的倍数变化相关性非常弱。总体通路水平的比较表明，AD和POCD是两种不同的疾病实体。同样，在经典的AD通路中，线粒体复合物和微管蛋白mRNA在POCD的海马体和皮质中均下调。POCD和AD的海马体可能共享相同的通路，如色氨酸代谢，但在吞噬体和转铁蛋白内吞作用通路中经历不同的病理变化。海马体网络中的核心簇主要富集在有丝分裂相关通路中。通过PCR检测到的感兴趣基因在海马体中的表达水平与高通量平台生成的结果具有良好的一致性。
尽管POCD和AD临床表现相似，但它们与不同的转录组变化相关。本研究为识别POCD的生物标志物和治疗靶点提供了有价值的资源。
