Whole transcriptome analysis of the hippocampus: toward a molecular portrait of epileptogenesis

Whole transcriptome analysis of the hippocampus: toward a molecular portrait of epileptogenesis

Autor Okamoto, Oswaldo Keith Autor UNIFESP Google Scholar
Janjoppi, Luciana Autor UNIFESP Google Scholar
Bonone, Filipe Meneguelli Autor UNIFESP Google Scholar
Pansani, Aline Priscila Autor UNIFESP Google Scholar
Silva, Alexandre Valotta da Autor UNIFESP Google Scholar
Scorza, Fulvio Alexandre Autor UNIFESP Google Scholar
Cavalheiro, Esper Abrão Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Background: Uncovering the molecular mechanisms involved in epileptogenesis is critical to better understand the physiopathology of epilepsies and to help develop new therapeutic strategies for this prevalent and severe neurological condition that affects millions of people worldwide.Results: Changes in the transcriptome of hippocampal cells from rats subjected to the pilocarpine model of epilepsy were evaluated by microarrays covering 34,000 transcripts representing all annotated rat genes to date. Using such genome-wide approach, differential expression of nearly 1,400 genes was detected during the course of epileptogenesis, from the early events post status epilepticus (SE) to the onset of recurrent spontaneous seizures. Most of these genes are novel and displayed an up-regulation after SE. Noteworthy, a group of 128 genes was found consistently hyper-expressed throughout epileptogenesis, indicating stable modulation of the p38MAPK, Jak-STAT, PI3K, and mTOR signaling pathways. in particular, up-regulation of genes from the TGF-beta and IGF-1 signaling pathways, with opposite effects on neurogenesis, correlate with the physiopathological changes reported in humans.Conclusions: A consistent regulation of genes functioning in intracellular signal transduction regulating neurogenesis have been identified during epileptogenesis, some of which with parallel expression patterns reported in patients with epilepsy, strengthening the link between these processes and development of epilepsy. These findings reveal dynamic molecular changes occurring in the hippocampus that may serve as a starting point for designing alternative therapeutic strategies to prevent the development of epilepsy after acquired brain insults.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Número do financiamento FAPESP: 02/01826-5
Data de publicação 2010-04-08
Publicado em Bmc Genomics. London: Biomed Central Ltd, v. 11, 12 p., 2010.
ISSN 1471-2164 (Sherpa/Romeo, fator de impacto)
Publicador Biomed Central Ltd
Extensão 12
Fonte http://dx.doi.org/10.1186/1471-2164-11-230
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000277049100001
Endereço permanente http://repositorio.unifesp.br/handle/11600/32468

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