Identification of Hub Genes and Pathways Associated with Ageing in Diabetic Encephalopathy Based on Transcriptome...

Area of Science:

• Neuroscience
• Genetics
• Metabolic Disorders

Background:

• Diabetic encephalopathy (DE) is a complication of diabetes mellitus.
• Diabetes accelerates brain ageing, leading to cognitive decline.
• Understanding the genetic and molecular mechanisms of DE-associated brain ageing is crucial.

Purpose of the Study:

• To identify key ageing-related differentially expressed genes (Ag-DEGs) in diabetic encephalopathy.
• To explore the roles and mechanisms of these genes in accelerating brain ageing in diabetes.
• To investigate the involvement of immune cells in diabetic brain ageing.

Main Methods:

• Transcriptome analysis of hippocampal tissue from db/db mice (a type 2 diabetes model).
• Identification of Ag-DEGs using GenAge and CellAge databases.
• Protein-protein interaction (PPI) network construction and hub gene identification using Cytoscape.
• Immune infiltration analysis of transcriptome data.

Main Results:

• 98 Ag-DEGs were identified, mainly involved in hypoxia, TNF-α/NF-κB, apoptosis, and P53 pathways.
• 14 hub genes were identified, including HDAC1, IGF2, EGR1, BCL2, FOS, ATM, EGF, PARP1, MAPK3, APOE, SOX2, CAV1, HSPA5, and NFKBIA.
• Significant differences in natural killer cells, resting mast cells, and plasma cells were observed in the diabetic brain.

Conclusions:

• This study identified key genes and pathways involved in diabetes-accelerated brain ageing in DE.
• The findings provide insights into the pathological mechanisms of diabetic brain ageing.
• Identified hub genes and immune cell alterations may serve as potential therapeutic targets.