Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients

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art_BANDO_Hippocampal_CA3_transcriptional_modules_associated_with_granule_cell_2021.PDF (5.93 MB)
Citações na Scopus
7
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE RESEARCH
Autores
PIMENTEL-SILVA, Luciana Ramalho
Citação
SCIENTIFIC REPORTS, v.11, n.1, article ID 10257, 16p, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules' main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.
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URI
https://observatorio.fm.usp.br/handle/OPI/41463
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE
Artigos e Materiais de Revistas Científicas - FM/MPE
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/36
Artigos e Materiais de Revistas Científicas - LIM/45
Artigos e Materiais de Revistas Científicas - LIM/62