Dataset Information

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

ABSTRACT:

Background

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.

Methods

First, 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.

Results

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.

Conclusion

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.

SUBMITTER: Wang YW

PROVIDER: S-EPMC9273890 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Wang Yi-Wei YW Wang Liang L Yuan Sheng-Jie SJ Zhang Yuan Y Zhang Xin X Zhou Le-Ting LT

Frontiers in aging neuroscience 20220628

<h4>Background</h4>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.<h4>Methods</h4>First, related databases were obtained from GEO, ArrayExpress, CNGB, and DDBJ repositories. <i>De novo</i> analysis was performed on the raw data using a uniform ...[more]

PMID: 35837480

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Project description:To understand multifactorial conditions such as Alzheimer's disease (AD) we need brain signatures that predict the impact of multiple pathologies and their interactions. To help uncover the relationships between pathology affected brain circuits and cognitive markers we have used mouse models that represent, at least in part, the complex interactions altered in AD, while being raised in uniform environments and with known genotype alterations. In particular, we aimed to understand the relationship between vulnerable brain circuits and memory deficits measured in the Morris water maze, and we tested several predictive modeling approaches. We used in vivo manganese enhanced MRI traditional voxel based analyses to reveal regional differences in volume (morphometry), signal intensity (activity), and magnetic susceptibility (iron deposition, demyelination). These regions included hippocampus, olfactory areas, entorhinal cortex and cerebellum, as well as the frontal association area. The properties of these regions, extracted from each of the imaging markers, were used to predict spatial memory. We next used eigenanatomy, which reduces dimensionality to produce sets of regions that explain the variance in the data. For each imaging marker, eigenanatomy revealed networks underpinning a range of cognitive functions including memory, motor function, and associative learning, allowing the detection of associations between context, location, and responses. Finally, the integration of multivariate markers in a supervised sparse canonical correlation approach outperformed single predictor models and had significant correlates to spatial memory. Among a priori selected regions, expected to play a role in memory dysfunction, the fornix also provided good predictors, raising the possibility of investigating how disease propagation within brain networks leads to cognitive deterioration. Our cross-sectional results support that modeling approaches integrating multivariate imaging markers provide sensitive predictors of AD-like behaviors. Such strategies for mapping brain circuits responsible for behaviors may help in the future predict disease progression, or response to interventions.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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