NS15P TRANSCRIPTIONAL REPRESSION IN A MOUSE MODEL OF EPILEPTOGENESIS

Abstract

Purpose To identify differentially expressed genes between normal and epileptic hippocampi with a two‐step transcriptome analysis using a mouse model of temporal lobe epilepsy.Method C57/Bl6 adult male mice were subjected to a rapid electrical amygdala kindling model. Large‐scale transcriptome profiling of the hippocampi was performed using LongSAGE. Comparison was performed using Fisher’s Exact test with functional categories assigned using GO annotation. Differential gene expression was independently confirmed using targeted real‐time quantitative PCR at various time‐points after kindling. Further confirmation was performed using immunoperoxidase staining and Western blots on selected genes.Results LongSAGE analysis revealed over 50 differentially expressed transcripts. A custom‐made microfluidics low‐density array card was made from this and other possible causative genes identified from the literature for real‐time PCR. qRT‐PCR on this card identified 38 differentially expressed genes between epileptic and normal mice hippocampi. There was clear evidence of transcriptional repression in the first 24 hours after kindling on qRT‐PCR and proteomic studies. GO annotation revealed down‐regulation in the majority of intracellular components, biological processes and molecular functions particularly those involved with metal binding activities, catalytic activities and protein binding.Conclusion There are significant differences in the gene expression between epileptic and normal hippocampi with marked transcriptional repression following epileptogenesis. This is especially evident in metabolic and morphologic genes located within membranes, parts of the cytoskeleton and the mitochondria.