Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction.

Ying Zhang,Qing Liu,Mohammed Al-Hawwas,Yue-Xin Liu,Feng-Xu Yu,Jiang Bian,Rui Deng,Isaac Bul Deng,Qiu-Xia Xiao

doi:10.3389/fnins.2018.00694

Abstract

Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.

Highlights

Postoperative cognitive dysfunction (POCD) is a severe central nervous system (CNS) complication in the cognitive function common in elderly patients after anesthesia and surgery
Clock Drawing Test (CDT) scores were noticeably lower in some patients and they were taken as POCD group compared with non-POCD group after 1 month of the surgery (Table 2)
The results presented 68 differentially expressed Long non-coding RNAs (lncRNAs) and 115 mRNAs in POCD group compared to non-POCD group. lnc-FAM53B-2_1 and Bioinformatics analyses were aimed to indicate the potential functions of the dysregulated lncRNAs that have been identified in our study

Summary

Introduction

Postoperative cognitive dysfunction (POCD) is a severe central nervous system (CNS) complication in the cognitive function common in elderly patients after anesthesia and surgery. Owing to differences in definitions and testing methods, the incidence of POCD has been reported globally with high prevalence. It includes central cholinergic system degradation, central inflammation (Hu et al, 2014), tau phosphorylation (Planel et al, 2007), β-amyloid deposition (Xu et al, 2012), and neuronal apoptosis (Vacas et al, 2014). POCD occurs in high prevalence and has severe effect on the affected patients (Witlox et al, 2010). There is no standard treatment of the disease or measures that can be taken to prevent or reduce the incidence of POCD (Pappa et al, 2017)

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