Transcriptomic analysis reveals potential targets associated with hippocampus vulnerability in spatial cognitive dysfunctionof type 2 diabetes mellitus rats.

Background: Cognitive dysfunction is one of the major complications of T2DM.However, the precise molecular mechanism underlying this relationship remains unclear. Present study aimed to identify potential predictors of cognitive dysfunction associated with T2DM specifically within the hippocampus.

Methods: T2DM was induced by a high-fat diet combined with streptozotocin injections. Morris water maze was employed to assess spatial cognitive ability. HE staining was used to evaluate neurons injury in hippocampus. Transcriptome sequencing was conducted on the hippocampus to identify potential genes. The results obtained from sequencing analysis werevalidated using qRT-PCR. GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways.

Results: Compared with CON rats, thespatial cognitive ability decreased in T2DM rats. Hippocampus neurons reduced in CA1 area of T2DM rats. In total, 123 DEGswere identified bytranscriptome sequencing, including 25 upregulated genes and 98 downregulated genes. The qRT-PCR results verified the RNA-seq. KEGG pathway analysis showed the major enriched pathways were TNF signaling pathway, arachidonic acid metabolism, AGE-RAGE signaling pathway in diabetic complications, and cellular senescence. GO analysis showed that DEGs involved in biological process were mainly related to vasculogenesis, response to hypoxia, regulation of cell proliferation and aging.

Conclusions: Our transcriptomic analysis reveals the "cellular senescence" signaling pathway may be implicated in T2DM-induced spatial cognitive dysfunction and Tgfbr2 may be the important DEG involved in this pathway, which will be the primary focus of our future research endeavors.