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Title: Gene Expression Profile in Genetic Models of Generalized Epilepsy: Clues into Underlying Mechanism
Citation: NEUROLOGY, v.78, suppl.1, 2012
Abstract: Objective: The aim of the present study was to characterize and compare the genetic profile of these strains through gene expression analysis. Background The Wistar Audiogenic Rat (WAR) is susceptible to audiogenic seizures, after high-intensity sound stimulation. Another genetic model is the generalized epilepsy with absence seizures (GEAS) rat. Design/Methods: We obtained total RNA from five susceptible WAR (hippocampus and corpora quadrigemina), and two resistant WAR, 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 and packages Affy and RankProd from Bioconductor. Overrepresented gene ontology categories were identified with DAVID software, and gene interactions and correlation networks were identified with Ingenuity Pathways Analysis software. Results: Enriched gene ontology identified in WAR were 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 development of the cochlear duct (Neurod1 up-regulated), and calcium and GABA receptor signaling (Gabra6 up-regulated). The main genes with differential expression and a possible biological role in epileptogenesis were, Apbb1 and Scn1A. 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 were endocrine system disorders, gastrointestinal disease, cell cycle and neurosystem development, which include genes such as Prlr, Hspb1, Igfpb2, CD74 and Fos. Conclusions: Our results clearly show a different molecular signature in the two genetic rat models analyzed, which may help to clarify the underlying molecular mechanism leading to seizure predisposition in these animals.
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Comunicações em Eventos - HC/ICHC
Instituto Central - HC/ICHC

Comunicações em Eventos - HC/InRad
Instituto de Radiologia - HC/InRad

Comunicações em Eventos - LIM/01
LIM/01 - Laboratório de Informática Médica

Comunicações em Eventos - LIM/44
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia

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