RNA-sequencing reveals immediate early genes upregulation in early stage of hippocampus in mouse model of Alzheimer’s disease

作者：Rina Takayanagi, Hiroko Matsunaga, Ran Wei, Ayaka Sugeno, Qianya Su, Takeru Ochi, Takaomi C Saido, Haruko Takeyama, Toshio Ohshima · 发表于：In Silico Research in Biomedicine · 年份：2026 · DOI：10.1016/j.insi.2026.100219 · 被引用次数：1 · 研究领域：Alzheimer's disease research and treatments、Dementia and Cognitive Impairment Research、Neuroinflammation and Neurodegeneration Mechanisms

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and the growing number of patients with AD has become a societal problem. Accumulation of amyloid-β (Aβ), one of the pathological features of AD, causes the activation of glial cells such as astrocytes and microglia. Cytokines released from these glial cells are involved in neuronal cell death; this process is known as neuroinflammation and is associated with the pathogenesis of AD. Previous studies have suggested that amyloid peptide oligomers are associated with the pathophysiology of AD before the formation of amyloid plaques. One approach to elucidate the pathophysiology of AD is transcriptome analysis to evaluate gene expression. The App NL-G-F mice used in this study (AD model mice) begin to accumulate Aβ at 2–3 months of age; however, in previous studies using these mice, gene expression analysis was performed only after 3 months of age. In the present study, we used hippocampal CA1, CA3, and DG neurons from 2.5-month-old wild-type (WT) and App NL-G-F male mice using the punching sampling method to examine differentially expressed genes (DEGs) using RNA-sequencing. Several DEGs were enriched in all the three hippocampal regions. Some genes were predominantly upregulated in the App NL-G-F hippocampus, where immediate early genes (IEGs) were enriched. These results suggest that IEGs are associated with neuronal hyperexcitability induced by Aβ oligomers.