Large-scale gene expression in genetic models of epilepsy

Abstract

The epilepsies are a group of chronic neurological diseases resulting from alterations in the brain associated or not with other neurological diseases. Since, affecting approximately 1% of the world population. The use of experimental models has contributed to a better understanding of the pathophysiology of epilepsy is in vitro and in vivo. A strain of mice WAR was established through genetic selection for audiogenic seizures, and despite having been very well characterized from the point of phenomenological and neurophysiological seen, are still gaps in knowledge regarding the genetic factors that determine susceptibility to crises.Our strategy will be based on the initial identification of genes with significant increase in the expression of lineage WAR animals that are susceptible to audiogenic seizures by stimulation. Then two candidate genes will be selected to undergo the technique of gene silencing by RNA interference in vivo (RNAi) to verify whether these genes affect susceptibility to audiogenic seizures, thus validating its possible role in susceptibility crises. The proposed strategy is unprecedented and after WAR validated the model could be applied to other models of genetic predisposition to epilepsy. Despite the proposal be challenging, we believe it is likely to be held within one master, since our group is experienced in the techniques of gene expression analysis in large scale and in vivo RNAi. In addition, we will have the cooperation of the partner group at FAPESP-FAPEMIG working for several years with the characterization neurophysiological model in WAR.