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

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

Abstract 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...

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Autores principales: Silvia Yumi Bando, Fernanda Bernardi Bertonha, Luciana Ramalho Pimentel-Silva, João Gabriel Mansano de Oliveira, Marco Antonio Duarte Carneiro, Mariana Hiromi Manoel Oku, Hung-Tzu Wen, Luiz Henrique Martins Castro, Carlos Alberto Moreira-Filho
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/5c0f18538296486aa81aab8bc692ee65
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spelling oai:doaj.org-article:5c0f18538296486aa81aab8bc692ee652021-12-02T15:43:23ZHippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients10.1038/s41598-021-89802-32045-2322https://doaj.org/article/5c0f18538296486aa81aab8bc692ee652021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89802-3https://doaj.org/toc/2045-2322Abstract 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.Silvia Yumi BandoFernanda Bernardi BertonhaLuciana Ramalho Pimentel-SilvaJoão Gabriel Mansano de OliveiraMarco Antonio Duarte CarneiroMariana Hiromi Manoel OkuHung-Tzu WenLuiz Henrique Martins CastroCarlos Alberto Moreira-FilhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Silvia Yumi Bando
Fernanda Bernardi Bertonha
Luciana Ramalho Pimentel-Silva
João Gabriel Mansano de Oliveira
Marco Antonio Duarte Carneiro
Mariana Hiromi Manoel Oku
Hung-Tzu Wen
Luiz Henrique Martins Castro
Carlos Alberto Moreira-Filho
Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
description Abstract 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.
format article
author Silvia Yumi Bando
Fernanda Bernardi Bertonha
Luciana Ramalho Pimentel-Silva
João Gabriel Mansano de Oliveira
Marco Antonio Duarte Carneiro
Mariana Hiromi Manoel Oku
Hung-Tzu Wen
Luiz Henrique Martins Castro
Carlos Alberto Moreira-Filho
author_facet Silvia Yumi Bando
Fernanda Bernardi Bertonha
Luciana Ramalho Pimentel-Silva
João Gabriel Mansano de Oliveira
Marco Antonio Duarte Carneiro
Mariana Hiromi Manoel Oku
Hung-Tzu Wen
Luiz Henrique Martins Castro
Carlos Alberto Moreira-Filho
author_sort Silvia Yumi Bando
title Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
title_short Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
title_full Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
title_fullStr Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
title_full_unstemmed Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
title_sort hippocampal ca3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/5c0f18538296486aa81aab8bc692ee65
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