Abstracts

Rationale: Wistar audiogenic rat (WAR) is a genetic epilepsy model susceptible to audiogenic seizures. Another genetic model we have recently identified is the generalized epilepsy with absence seizures (GEAS) rat. The aim of the present study was to characterize and compare gene expression profile of these two strains in order to determine whether they share a common genetic susceptibility to seizures. Methods: We obtained total RNA from five susceptible WAR (hippocampus and corpora quadrigemina), and five control Wistar, as well as from hippocampus of three GEAS rats and three control Wistar. Gene expression analysis was performed using the GeneChip® Rat Genome 230 2.0 Array (Affymetrix™), and analyzed in R environment using the Affy and RankProd packages from Bioconductor. Overrepresented gene ontology categories were identified with DAVID software, and gene interactions and correlation networks were identified with MetaCore software. Results: Enriched gene ontology classes identified in WAR were mainly involved in neuronal development and differentiation, regulation of synaptic transmission and neuron projection, as well as cell-cell signaling. The most active signaling pathways were, signal transduction and calcium signaling. The main genes with differential expression and a possible biological role in epileptogenesis were potassium and sodium channel, glutamate receptor and GABA receptor. In the GEAS rats we found differential expression of genes related to central nervous system development, activation of MAPK transcription factors, neuronal migration and apoptosis, such as Nrsn1, Hspb1, Fos, Twist1 and Krt18. The top enriched gene ontology categories included signal peptide, extracellular region and antigen processing and presentation. Among the most activated signaling pathways was neurosystem development. Conclusions: Our results clearly show a different molecular signature in the two genetic rat models analyzed. Our results are the first step to clarify the underlying molecular mechanism that leads to predisposition to seizures in these genetic animal models.