■围手术期神经认知障碍(PND)是指围手术期的神经认知异常,这对老年患者来说是一个巨大的挑战,并与发病率和死亡率的增加有关。我们的研究表明,长链非编码RNA(lncRNAs)调节麻醉后老年海马的线粒体功能和衰老相关病理,和lncRNAs与多个神经变性相关。然而,lncRNAs在PND相关病理过程中的调节作用尚不清楚.
■将总共18个月的小鼠分配到对照组和手术(PND)组,PND组小鼠接受七氟烷麻醉和剖腹手术。通过恐惧条件测试评估认知功能。分离海马RNA进行测序,构建了lncRNA和microRNA文库,mRNA被鉴定,进行基因本体论(GO)分析,并建立了lncRNA-microRNA-mRNA网络。进行qPCR用于基因表达验证。
■总共312个差异表达(DE)lncRNAs,340不确定编码潜力(TUCP)的去转录本,在组间的海马中鉴定出2,003个DEmRNA。lncRNA-microRNA-mRNA竞争内源RNA(ceRNA)网络与29个DElncRNA,90microRNAs,493DMRNAs,148个lncRNA-microRNA相互作用对,794microRNA-mRNA相互作用对,和110个lncRNA-mRNA共表达对。获得了795个GO项。根据所涉及的病理过程的频率,BP术语分为八类:神经系统交替,神经元发育,新陈代谢交替,免疫和神经炎症,凋亡和自噬,蜂窝通信,分子修饰,和行为改变。构建了这些病理类别中的LncRNA-microRNA-mRNAceRNA网络,并揭示了涉及的途径和靶向基因。这些ceRNA网络中最相关的lncRNA包括RP23-65G6.4、RP24-396L14.1、RP23-251I16.2、XLOC_113622、RP24-496E14.1等。,这些ceRNA网络中最相关的mRNA包括Dlg4(突触功能),Avp(吸脂性),Islr2(突触功能),Hcrt(清醒行为的调节),TNC(神经递质摄取)。
■总之,我们在小鼠PND发育过程中构建了lncRNA相关的ceRNA网络,探索lncRNAs在小鼠海马多个病理过程中的作用,并为PND的潜在机制和治疗基因靶标提供了见解。
UNASSIGNED: Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities during perioperative period, which are a great challenge for elderly patients and associated with increased morbidity and mortality. Our studies showed that long non-coding RNAs (lncRNAs) regulate mitochondrial function and aging-related pathologies in the aged hippocampus after anesthesia, and lncRNAs are associated with multiple neurodegenerations. However, the regulatory role of lncRNAs in PND-related pathological processes remains unclear.
UNASSIGNED: A total of 18-month mice were assigned to control and surgery (PND) groups, mice in PND group received sevoflurane anesthesia and laparotomy. Cognitive function was assessed with fear conditioning test. Hippocampal RNAs were isolated for sequencing, lncRNA and microRNA libraries were constructed, mRNAs were identified, Gene Ontology (GO) analysis were performed, and lncRNA-microRNA-mRNA networks were established. qPCR was performed for gene expression verification.
UNASSIGNED: A total of 312 differentially expressed (DE) lncRNAs, 340 DE-Transcripts of Uncertain Coding Potential (TUCPs), and 2,003 DEmRNAs were identified in the hippocampus between groups. The lncRNA-microRNA-mRNA competing endogenous RNA (ceRNA) network was constructed with 29 DElncRNAs, 90 microRNAs, 493 DEmRNAs, 148 lncRNA-microRNA interaction pairs, 794 microRNA-mRNA interaction pairs, and 110 lncRNA-mRNA co-expression pairs. 795 GO terms were obtained. Based on the frequencies of involved pathological processes, BP terms were divided into eight categories: neurological system alternation, neuronal development, metabolism alternation, immunity and neuroinflammation, apoptosis and autophagy, cellular communication, molecular modification, and behavior changes. LncRNA-microRNA-mRNA ceRNA networks in these pathological categories were constructed, and involved pathways and targeted genes were revealed. The top relevant lncRNAs in these ceRNA networks included RP23-65G6.4, RP24-396L14.1, RP23-251I16.2, XLOC_113622, RP24-496E14.1, etc., and the top relevant mRNAs in these ceRNA networks included Dlg4 (synaptic function), Avp (lipophagy), Islr2 (synaptic function), Hcrt (regulation of awake behavior), Tnc (neurotransmitter uptake).
UNASSIGNED: In summary, we have constructed the lncRNA-associated ceRNA network during PND development in mice, explored the role of lncRNAs in multiple pathological processes in the mouse hippocampus, and provided insights into the potential mechanisms and therapeutic gene targets for PND.