Large-scale gene expression in genetic models of epilepsy

Author(s)

Alexandre Hilário Berenguer de Matos

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2013-02-20

Examining board members

Íscia Teresinha Lopes Cendes; Luciene Covolan; Licio Augusto Velloso

• Advisor: Íscia Teresinha Lopes Cendes

Abstract

Wistar audiogenic rat (WAR) is a genetic epilepsy model susceptible to audiogenic seizures, after high-intensity sound stimulation. 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 the genetic profile of these two strains using gene expression analysis. Experiments were performed initially using microarray technology followed by quantitative real-time PCR. Results were analyzed in R environment using the Affy and RankProd packages from Bioconductor, using the algorithm MAS 5 we normalized the arrays and calculated the signal intensity and the detection (presence or absence of expression), after the detection, transcripts which were absent in all samples were removed. For statistical analysis we used the Rank Product test, which is biologically motivated and designed to test and detect differentially expressed genes in replicated microarray experiments. This is a simple non-parametric statistical method based on ranks of fold changes. We used a p-value ? 0.01 and a pfp ? 0.05 in order to consider a given transcript to be differentially expressed Overall, the results show a different molecular signature in the two genetic rat models analyzed, since different enriched gene ontology categories were found. However, there was some overlap in the list of genes differentially expressed found in both models when comparing to controls. In addition, we found that two important molecular pathways for epileptogenesis: GABAergic neurotransmission and: Neurophysiological process NMDA-dependent postsynaptic long-term potentiation in CA1 hippocampal neurons, were found to be present in both models when combining data from WAR and GEAS animals. In conclusion, our results clearly show the heterogeneous and intricate nature of the molecular mechanisms involved in epileptogenesis as well as the importance of studies looking at different regulatory pathways at once, in order to better appreciate this complexity (AU)

• FAPESP's process: 10/13104-0 - Large-scale gene expression in genetic models of epilepsy
• Grantee: Alexandre Hilário Berenguer de Matos
• Support Opportunities: Scholarships in Brazil - Master