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

OBJECTIVE To 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 3h, 12h, and 24h, 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 3h, 12h, and 24h groups. Although 56 overlapping up-regulated genes and 2 down-regulated genes were identified in 3h, 12h, and 24h 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 3h, 12h, and 24h groups, respectively. As for metabolism, there were 2 specific altered genes in the 3h group (casp8ap2 and mmp2), 6 in the 24h group (daxx, gadd45a, adamts1, adcy8, cyp51, dusp16), but none in the 12h 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 3h and 12h, 12h and 24h, and 3h and 24h 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.

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