Hippocampal transcriptome analysis reveals mechanisms of cognitive impairment in beagle dogs with type 1 diabetes

Abstract

Diabetic encephalopathy is a common complication of type 1 diabetes. However, there have been few studies on cognitive impairment and hippocampal damage in type 1 diabetes mellitus (T1DM) using dogs as experimental animals. To investigate the effects of diabetes on the CNS, 40 adult beagles were divided into streptozotocin/alloxan type 1 diabetes model and control groups. The duration of diabetes in the model group was 120 days. A cognitive dysfunction scale was used to assess cognitive function. Hematoxylin and eosin and Golgi-Cox staining methods were used to observe morphological damage to the hippocampus. Transcriptomics was used to investigate differential gene expression in the hippocampus. The results showed that the cognitive dysfunction score of the model group was significantly higher than that of the control group. In addition, the number of normal neurons, the complexity of dendritic morphology, and the density of dendritic spines were decreased in the hippocampus of diabetic dogs. A total of 672 differentially expressed genes (DEGs) were identified, 289 of which were upregulated, and 383 were downregulated. Modified genes included DBH, IGFBP2, AVPR1A, and DRAXIN. In conclusion, type 1 diabetic dogs exhibit cognitive dysfunction. The DEGs were mainly enriched in metabolic, PI3K-Akt signaling, and neuroactive ligand-receptor interaction pathways.