Meta-Analysis of Kindling-Induced Gene Expression Changes in the Rat Hippocampus

Numerous studies have been performed to examine gene expression patterns in the rodent hippocampus in the kindling model of epilepsy. However, recent reviews of this literature have revealed limited agreement among studies. Because this conclusion was based on retrospective comparison of reported "hit lists" from individual studies, we hypothesized that re-analysis of the original expression data would help address this concern. In this paper, we reanalyzed four genome-wide expression studies of excitotoxin-induced kindling in rat and performed a statistical meta-analysis. The meta-analysis revealed over 800 genes which show significant change in expression 24 h after initial seizure induction, and 59 genes altered after 10 days. To evaluate our results in light of previous work, we assembled a reference list of genes formed from a consensus of the published literature. Our profiles include most of the genes in this reference list, and most of the additional genes are from pathways or biological processes previously recognized to be altered in kindling. In addition our results emphasized expression changes in lipid metabolism and protein degradation pathways. We conclude that a cautious re-analysis of published expression data can help illuminate genes and pathways underling kindling. Supplementary Material is available at http://www.chibi.ubc.ca/faculty/pavlidis/meta-analysis-of-brain-kindling/