Genomics

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Transcriptome profiling of miRNA and mRNA of the cortex in a rat model of Vascular dementia by RNA-sequencing


ABSTRACT: In this study, we investigated the miRNA and mRNA profiling of the cortex of rat model of vascular dementia (VaD) to analyze the regulatory mechanism in the pathology of VaD involved by miRNAs, transcription factors (TFs), and corresponding target genes. As a validated model of VaD, rats suffering from bilateral common carotid artery occlusion (2VO) were used in the present study and the reliability of this model was examined by the Morris water maze (MWM) test and the Nissl staining. Overall, results showed that rats with 2VO presented declined learning and memory capabilities in the MWM test and neuronal loss in the hippocampus and cortex indicated by Nissl-staining compared to sham rats. DEGs, DEMs, and DETFs were discriminated between rats with 2VO and sham rats in the cortex, illustrated by 13 aberrantly-expressed miRNAs, 805 mRNAs, and 63 TFs. Further network analysis revealed that 7 target genes, 5 miRNAs, and 10 TFs were the key molecule in the miRNA-TF-gene network related to VaD. Gene Ontology (GO) and pathway enrichment analyses of these VaD-related transcripts showed that these differently changed genes mostly got involved in PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, calcium signaling pathway, and Wnt signaling pathway, along with central locations around cell membrane, exerting function such as growth factor binding, integrin binding, and extracellular matrix structural constituent, with representative biological processes like vasculature development, cell-substrate adhesion, cellular response to growth factor stimulus, and synaptic transmission. In conclusion, these results will help us understand the underlying regulatory mechanisms of miRNA-TF-genes in pathogenesis and provide potential therapeutic targets for the treatment of VaD.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE199508 | GEO | 2022/09/15

REPOSITORIES: GEO

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