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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Temporal analysis of hippocampal CA3 gene coexpression networks in a rat model of febrile seizures

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Autor(es):
Azevedo, Hatylas [1] ; Khaled, Nathalia Amato [1] ; Santos, Paula [1] ; Bertonha, Fernanda Bernardi [1] ; Moreira-Filho, Carlos Alberto [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Sao Paulo FMUSP, Dept Pediat, Fac Med, BR-05403000 Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Disease Models & Mechanisms; v. 11, n. 1 JAN 2018.
Citações Web of Science: 3
Resumo

Complex febrile seizures during infancy constitute an important risk factor for development of epilepsy. However, little is known about the alterations induced by febrile seizures that make the brain susceptible to epileptic activity. In this context, the use of animal models of hyperthermic seizures (HS) could allow the temporal analysis of brain molecular changes that arise after febrile seizures. Here, we investigated temporal changes in hippocampal gene coexpression networks during the development of rats submitted to HS. Total RNA samples were obtained from the ventral hippocampal CA3 region at four time points after HS at postnatal day (P) 11 and later used for gene expression profiling. Temporal endpoints were selected for investigating the acute (P12), latent (P30 and P60) and chronic (P120) stages of the HS model. A weighted gene coexpression network analysis was used to characterize modules of coexpressed genes, as these modules might contain genes with similar functions. The transcriptome analysis pipeline consisted of building gene coexpression networks, identifying network modules and hubs, performing gene-trait correlations and examining changes in module connectivity. Modules were functionally enriched to identify functions associated with HS. Our data showed that HS induce changes in developmental, cell adhesion and immune pathways, such as Wnt, Hippo, Notch, Jak-Stat and Mapk. Interestingly, modules involved in cell adhesion, neuronal differentiation and synaptic transmission were activated as early as 1 day after HS. These results suggest that HS trigger transcriptional alterations that could lead to persistent neurogenesis, tissue remodeling and inflammation in the CA3 hippocampus, making the brain prone to epileptic activity. (AU)

Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
Beneficiário:Roberto Marcondes Cesar Junior
Linha de fomento: Auxílio à Pesquisa - Temático