Research ReportDynamic variation of genes profiles and pathways in the hippocampus of ischemic mice: A genomic study

ObjectiveTo reveal the potential time-sequential molecular mechanism in the hippocampus of ischemia-reperfusion mice, so as to provide pertinent evidence for differential treatment during different phases after cerebral ischemia-reperfusion injury. Methods Seventy-five male Kunming mice were randomly divided into four groups: sham, ischemia and reperfusion for 3 h, 12 h, and 24 h, respectively. A cDNA microarray involving 374 cDNA ischemia-related genes, selected from the Science STKE database, was performed to detect the gene expression profiles. All data analyses were performed in the FDA ArrayTrack system. Data were also uploaded to the KEGG database (http://www.genome.jp/kegg/) to analyze the genetic pathways. Results Clustering and principal component analyses showed clear boundaries in the differentially expressed genes among the 3 h, 12 h, and 24 h groups. Although 56 overlapping up-regulated genes and 2 down-regulated genes were identified in 3 h, 12 h, and 24 h groups, the sequence variation of CA1 neurons and gene expression profiles also existed in all groups. Based on the total number of altered genes, the top 3 GO categories were metabolism, signal and cell cycle, which shared 8, 11 and 5 overlapping genes in 3 h, 12 h, and 24 h groups, respectively. As for metabolism, there were 2 specific altered genes in the 3 h group (casp8ap2 and mmp2), 6 in the 24 h group (daxx, gadd45a, adamts1, adcy8, cyp51, dusp16), but none in the 12 h group. Based on the KEGG database analysis, 18 overlapping pathways were detected in the three groups; and 1, 12 and 2 overlapping pathways were noted between the 3 h and 12 h, 12 h and 24 h, and 3 h and 24 h comparisons, respectively. The gene expressions of Caspase 2 and Rgs6 were identified by real-time RT-PCR, which was consistent with the results of microarray analysis. Conclusion Overlapping and variable genes and pathways demonstrate the time-sequential molecular mechanism in the hippocampus of ischemic mice, which may provide evidence for rational treatment during different phases after cerebral ischemia-reperfusion injury.

Research Highlights►Study the dynamic pathological mechanism of cerebral ischemia from genome. ►Gene expression and pathways present time sequence, which suggest treating with time. ►Many genes and pathways related to ischemia-reperfusion injury had been found first.