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

Autor(es)

Bando, Silvia Yumi ^[1] ; Bertonha, Fernanda Bernardi ^[1] ; Pimentel-Silva, Luciana Ramalho ^[2] ; Mansano de Oliveira, Joao Gabriel ^[3] ; Duarte Carneiro, Marco Antonio ^[3] ; Manoel Oku, Mariana Hiromi ^[3] ; Wen, Hung-Tzu ^[4] ; Martins Castro, Luiz Henrique ^[3] ; Moreira-Filho, Carlos Alberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pediat, Fac Med, BR-05403900 Sao Paulo, SP - Brazil

^[2] Univ Estadual Campinas, Dept Neurol, UNICAMP, Fac Ciencias Med, BR-13083887 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Dept Neurol, Fac Med, BR-05403900 Sao Paulo, SP - Brazil

^[4] Hosp Clin FMUSP, Epilepsy Surg Grp, BR-05403900 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 MAY 13 2021.
• Citações Web of Science: 0

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. (AU)

• Processo FAPESP: 15/22308-2 - Representações intermediárias em Ciência Computacional para descoberta de conhecimento
• Beneficiário: Roberto Marcondes Cesar Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 05/56446-0 - Estudos de ressonância magnética de alta resolução e imagem de receptores em epilepsia refratária do lobo temporal: análises in vivo e ex vivo
• Beneficiário: Edson Amaro Junior
• Modalidade de apoio: Auxílio à Pesquisa - Programa CINAPCE - Temático