Analysis of Adult Cerebral Cortex and Hippocampus Transcriptomes Reveals Unique Molecular Changes in the Ts1Cje Mouse Model of Down Syndrome

We investigated gene expression and functional differences between Ts1Cje mice and wild-type (WT) littermates in adult cerebral cortex and hippocampus. These two brain regions are affected in people with Down syndrome, but have not been previously molecularly characterized in Ts1Cje mice. Total RNA was prepared from the brains of 8-10-week-old Ts1Cje mice (n=6) and WT littermates (n=5) and hybridized to Affymetrix 1.0 ST gene mouse arrays. Differentially regulated genes were identified and used to perform in silico functional analyses to better characterize dysregulated pathways in both brain regions. Hippocampus had more significantly differentially expressed genes compared with cortex (30 vs. 7 at a Benjamini-Hochberg false discovery rate of 20%). We identified novel genes that were differentially regulated in adult brains, including Cyb5r1, Fsbp, Vmn2r110, Snd1 and Zhx2. Functional analyses in Ts1Cje mice highlighted the importance of NFAT signaling, oxidative stress, neuroinflammation and olfactory perception via G-protein signaling. In a comparison of adult Ts1Cje and WT brains, we identified new genes and pathway differences in the cortex and hippocampus. Our analyses identified physiologically relevant pathways that can serve as targets for the development of future treatments to improve neurocognition in Down syndrome.