Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models

BackgroundPostoperative 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...

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Main Authors: Yi-Wei Wang, Liang Wang, Sheng-Jie Yuan, Yuan Zhang, Xin Zhang, Le-Ting Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2022.900350/full
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author Yi-Wei Wang
Liang Wang
Sheng-Jie Yuan
Yuan Zhang
Xin Zhang
Xin Zhang
Le-Ting Zhou
author_facet Yi-Wei Wang
Liang Wang
Sheng-Jie Yuan
Yuan Zhang
Xin Zhang
Xin Zhang
Le-Ting Zhou
author_sort Yi-Wei Wang
collection DOAJ
description BackgroundPostoperative 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.MethodsFirst, related databases were obtained from GEO, ArrayExpress, CNGB, and DDBJ repositories. De novo 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.ResultsThere 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.ConclusionPOCD 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.
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spelling doaj.art-bf0ca8a76c3c4d779a0e7c8107a73dfc2022-12-22T00:21:56ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-06-011410.3389/fnagi.2022.900350900350Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal ModelsYi-Wei Wang0Liang Wang1Sheng-Jie Yuan2Yuan Zhang3Xin Zhang4Xin Zhang5Le-Ting Zhou6Department of Anesthesiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Internal Medicine, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Anesthesiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Internal Medicine, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Anesthesiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, ChinaDepartment of Anesthesiology, Center for Translational Pain Medicine, Duke University School of Medicine, Durham, NC, United StatesDepartment of Internal Medicine, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, ChinaBackgroundPostoperative 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.MethodsFirst, related databases were obtained from GEO, ArrayExpress, CNGB, and DDBJ repositories. De novo 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.ResultsThere 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.ConclusionPOCD 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.https://www.frontiersin.org/articles/10.3389/fnagi.2022.900350/fullpostoperative cognitive dysfunctionAlzheimer’s diseasebioinformaticstranscriptomicshigh throughput data
spellingShingle Yi-Wei Wang
Liang Wang
Sheng-Jie Yuan
Yuan Zhang
Xin Zhang
Xin Zhang
Le-Ting Zhou
Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models
Frontiers in Aging Neuroscience
postoperative cognitive dysfunction
Alzheimer’s disease
bioinformatics
transcriptomics
high throughput data
title Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models
title_full Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models
title_fullStr Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models
title_full_unstemmed Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models
title_short Postoperative Cognitive Dysfunction and Alzheimer’s Disease: A Transcriptome-Based Comparison of Animal Models
title_sort postoperative cognitive dysfunction and alzheimer s disease a transcriptome based comparison of animal models
topic postoperative cognitive dysfunction
Alzheimer’s disease
bioinformatics
transcriptomics
high throughput data
url https://www.frontiersin.org/articles/10.3389/fnagi.2022.900350/full
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