Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND

Perioperative neurocognitive disorders (PND) are common complications observed in surgical patients, but there are no effective treatments and the detailed mechanisms remain largely unknown. In this study, transcriptome analysis was performed to investigate the hippocampal changes after surgery and...

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Main Authors: Xuwu Xiang, Yang Yu, Xiaodong Tang, Manli Chen, Yueying Zheng, Shengmei Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00149/full
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author Xuwu Xiang
Yang Yu
Xiaodong Tang
Manli Chen
Yueying Zheng
Shengmei Zhu
author_facet Xuwu Xiang
Yang Yu
Xiaodong Tang
Manli Chen
Yueying Zheng
Shengmei Zhu
author_sort Xuwu Xiang
collection DOAJ
description Perioperative neurocognitive disorders (PND) are common complications observed in surgical patients, but there are no effective treatments and the detailed mechanisms remain largely unknown. In this study, transcriptome analysis was performed to investigate the hippocampal changes after surgery and underlying molecular mechanisms of PND. Tibial fracture surgery was performed in 3–4 months old C57BL/6J mice to mimic human orthopedic surgery. We demonstrated that memory consolidation of the hippocampal-dependent trace-fear conditioning task was significantly impaired. By using ELISA, a significant elevated IL-6 was observed both in circulating system and central nervous system and peaked at 6 h post-surgery, but transiently returned to baseline thereafter. Hippocampus were collected at 6 h post-surgery then processed for RNA-Seq. A total of 268 genes were screened differentially expressed between the Surgery and Control group, including 170 up-regulated genes and 98 down-regulated genes. By functional enrichment analysis of differently expressed genes, several KEGG pathways involved in inflammatory mediator regulation of TRP channels, neuroactive ligand-receptor interaction and cholinergic synapse were overrepresented. Quantitative real-time PCR confirmed 15 dysregulated genes of interest. These results provide a comprehensive insight into global gene expression changes during the acute presence of hippocampal inflammation and a better understanding on early stage of PND.
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spelling doaj.art-9ab9c8e158b440a7b08969e6ba6198602022-12-22T01:43:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-02-011010.3389/fimmu.2019.00149432291Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PNDXuwu XiangYang YuXiaodong TangManli ChenYueying ZhengShengmei ZhuPerioperative neurocognitive disorders (PND) are common complications observed in surgical patients, but there are no effective treatments and the detailed mechanisms remain largely unknown. In this study, transcriptome analysis was performed to investigate the hippocampal changes after surgery and underlying molecular mechanisms of PND. Tibial fracture surgery was performed in 3–4 months old C57BL/6J mice to mimic human orthopedic surgery. We demonstrated that memory consolidation of the hippocampal-dependent trace-fear conditioning task was significantly impaired. By using ELISA, a significant elevated IL-6 was observed both in circulating system and central nervous system and peaked at 6 h post-surgery, but transiently returned to baseline thereafter. Hippocampus were collected at 6 h post-surgery then processed for RNA-Seq. A total of 268 genes were screened differentially expressed between the Surgery and Control group, including 170 up-regulated genes and 98 down-regulated genes. By functional enrichment analysis of differently expressed genes, several KEGG pathways involved in inflammatory mediator regulation of TRP channels, neuroactive ligand-receptor interaction and cholinergic synapse were overrepresented. Quantitative real-time PCR confirmed 15 dysregulated genes of interest. These results provide a comprehensive insight into global gene expression changes during the acute presence of hippocampal inflammation and a better understanding on early stage of PND.https://www.frontiersin.org/article/10.3389/fimmu.2019.00149/fullcognitive dysfunctionsurgeryhippocampusneuroinflammationRNA-Seq
spellingShingle Xuwu Xiang
Yang Yu
Xiaodong Tang
Manli Chen
Yueying Zheng
Shengmei Zhu
Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND
Frontiers in Immunology
cognitive dysfunction
surgery
hippocampus
neuroinflammation
RNA-Seq
title Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND
title_full Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND
title_fullStr Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND
title_full_unstemmed Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND
title_short Transcriptome Profile in Hippocampus During Acute Inflammatory Response to Surgery: Toward Early Stage of PND
title_sort transcriptome profile in hippocampus during acute inflammatory response to surgery toward early stage of pnd
topic cognitive dysfunction
surgery
hippocampus
neuroinflammation
RNA-Seq
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00149/full
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