Transcriptome sequencing and bioinformatics analysis of hippocampus in aged rats with cognitive decline.

Abstract

Age-related cognitive decline poses significant challenges to healthy aging, yet its underlying molecular mechanisms remain poorly understood. In this study, we employed Morris Water Maze and hippocampal transcriptome analysis to investigate age-related cognitive decline in a rat model. Aged rats (RA) exhibited significant spatial memory deficits compared to young rats (RY). Transcriptome analysis identified ‌121 differentially expressed genes (DEGs)‌ in the hippocampus ‌of‌ RA group compared with RY group, including ‌54 up-regulated and 67 down-regulated genes. The qRT-PCR validation revealed significant up-regulation of Cd74 and Cd4 expression, along with marked down-regulation of Col1a1, Col3a1, and Serpine1 expression in RA group compared to RY group. Bioinformatics analysis revealed these DEGs were enriched in the biological processes of chronic inflammation, loss of proteostasis, and extracellular matrix pathways. These findings suggest hippocampal transcriptomic alterations may contribute to cognitive aging, providing potential predictors for cognitive function and ‌a‌ foundation for exploring molecular mechanisms.