Gene expression profile suggests different mechanisms underlying sporadic and familial mesial temporal lobe epilepsy

Autor(es)

Maurer-Morelli, Claudia, V ; de Vasconcellos, Jaira F. ; Bruxel, Estela M. ; Rocha, Cristiane S. ; do Canto, Amanda M. ; Tedeschi, Helder ; Yasuda, Clarissa L. ; Cendes, Fernando ; Lopes-Cendes, Iscia

• Tipo de documento: Artigo Científico
• Fonte: Experimental Biology and Medicine; v. 247, n. 24, p. 18-pg., 2022-10-19.

Resumo

Most patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) have hippocampal sclerosis on the postoperative histopathological examination. Although most patients with MTLE do not refer to a family history of the disease, familial forms of MTLE have been reported. We studied surgical specimens from patients with MTLE who had epilepsy surgery for medically intractable seizures. We assessed and compared gene expression profiles of the tissue lesion found in patients with familial MTLE (n = 3) and sporadic MTLE (n = 5). In addition, we used data from control hippocampi obtained from a public database (n = 7). We obtained expression profiles using the Human Genome U133 Plus 2.0 (Affymetrix) microarray platform. Overall, the molecular profile identified in familial MTLE differed from that in sporadic MTLE. In the tissue of patients with familial MTLE, we found an over-representation of the biological pathways related to protein response, mRNA processing, and synaptic plasticity and function. In sporadic MTLE, the gene expression profile suggests that the inflammatory response is highly activated. In addition, we found enrichment of gene sets involved in inflammatory cytokines and mediators and chemokine receptor pathways in both groups. However, in sporadic MTLE, we also found enrichment of epidermal growth factor signaling, prostaglandin synthesis and regulation, and microglia pathogen phagocytosis pathways. Furthermore, based on the gene expression signatures, we identified different potential compounds to treat patients with familial and sporadic MTLE. To our knowledge, this is the first study assessing the mRNA profile in surgical tissue obtained from patients with familial MTLE and comparing it with sporadic MTLE. Our results clearly show that, despite phenotypic similarities, both forms of MTLE present distinct molecular signatures, thus suggesting different underlying molecular mechanisms that may require distinct therapeutic approaches. (AU)

• Processo FAPESP: 10/17440-5 - Análise de expressão gênica em larga escala na epilepsia de lobo temporal mesial
• Beneficiário: Jaíra Ferreira de Vasconcellos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/25948-3 - Análise de sinaptossomos isolados do hipocampo de pacientes com Epilepsia Do Lobo Temporal Mesial utilizando ferramentas de proteômica e metabolômica
• Beneficiário: Amanda Morato Do Canto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/03254-7 - ESTUDO DE ASSOCIAÇÃO DE VARREDURA GENÔMICA BASEADA NA EXPRESSÃO GÊNICA (eGWAS) EM EPILEPSIA DE LOBO TEMPORAL MESIAL
• Beneficiário: Estela Maria Bruxel
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 08/54789-6 - Análise da expressão gênica na epilepsia de lobo temporal mesial através da técnica de chip de DNA em espécimes cirúrgicos hipocampais de pacientes refratários à medicação e em tecido cerebral de modelos
• Beneficiário: Cláudia Vianna Maurer Morelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 05/56578-4 - Centro multimodal de neuroimagens para estudos em epilepsia
• Beneficiário: Fernando Cendes
• Modalidade de apoio: Auxílio à Pesquisa - Programa CINAPCE - Temático