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Transcriptome analysis in animal models of mesial temporal lobe epilepsy

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Author(s):
Alexandre Hilário Berenguer de Matos
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Íscia Teresinha Lopes Cendes; Marcondes Cavalcante Franca Junior; Ângela Cristina do Valle; Clarissa Lin Yasuda; Roger Walz
Advisor: Íscia Teresinha Lopes Cendes; Andre Schwambach Vieira
Abstract

Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the development of seizures and by histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). It is well known that gene expression profile of specific tissue provides relevant biological information about molecular mechanisms potentially involved in complex biological phenomena. Recently, it has been recognized that due to the marked heterogeneity of gene expression in a different subset of cells, it is important to take sub-regional specificities when studying gene expression, especially in the central nervous system. We used RNA sequencing analysis to determine the profile of gene expression in the hippocampus dentate gyrus (DG) and Cornu Ammonis 3 (CA3) in an animal model of mesial temporal lobe epilepsy induced by pilocarpine. The high-throughput RNA sequencing was performed in tissue obtained from the dorsal and ventral DG and CA3, as well as the intermediate CA3, by laser-microdissection in Wistar rats. We evaluated the gene expression profile and the enriched signaling biological processes. Our results indicate that there were many differentially regulated genes, some of which were specific to each sub-regions of the hippocampus in the pilocarpine rats. However, we identified some major signaling biological processes that were enriched in all layers and areas examined, such as inflammation, axon guidance, neuronal activity and synaptic function. The data presented highlights the importance of high-throughput transcriptome analysis in the study of complex disorders such as epilepsy, and the advantage of obtaining tissue from delimitated areas to fully appreciate the large biological heterogeneity of different cell populations within the central nervous system. Our results suggest a predominance of the dorsal region in the neuronal electrical activity and axonal guidance. Furthermore, we identified an interaction among several molecular components leading to the epileptogenesis in this animal model that displays widespread hippocampal damage (AU)

FAPESP's process: 13/08635-5 - TRANSCRIPTOME ANALYSIS IN ANIMAL MODELS OF MESIAL TEMPORAL LOBE EPILEPSY
Grantee:Alexandre Hilário Berenguer de Matos
Support Opportunities: Scholarships in Brazil - Doctorate