Abstract: Objective To investigate the dysregulated genes, pathways and networks involved in type 2 diabetes-derived brain dysfunctions via performing whole transcriptome sequencing on the cerebral cortex of db/db and wild-type (WT) mice. Methods Male db/db and WT mice were divided into two groups (n=9). The body weight and blood glucose were measured at week 8 and 24. The 24-week-old animals were sacrificed for cerebral cortex collection. RNA-sequencing and analysis of differentially expressed genes (DEGs), GO functional enrichment, KEGG pathway enrichment and PPI network were performed. Results A total of 306 differential transcripts, including 178 up-regulated and 128 down-regulated ones were identified in the db/db mice as compared to WT ones. Among all differentially expressed genes, 43 genes (such as Clcnka and Trim17) were found to be up-regulated and 59 genes (such as Arih1 and Nectin-3) were down-regulated. The protein-protein interaction network was constructed with thirteen nodes as hub genes. All the nodes were down-regulated genes and majorly belonged to mitochondrially encoded families. The GO functional enrichment showed changes in various categories as compared to WT. KEGG enrichment analysis revealed that target genes were mainly enriched in metabolic pathways, Parkinson's disease, Alzheimer's disease, and the involved DEGs mainly regulate oxidative phosphorylation process. Conclusions The relationship between type 2 diabetes and central nervous system impairments, and the potentially related genes, pathways and networks are identified.

Key words: transcriptome sequencing, type 2 diabetes, cortex, brain dysfunction