Benchmarking the proteomic profile of animal models of mesial temporal epilepsy

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Canto, Amanda M. ; Godoi, Alexandre B. ; Matos, Alexandre H. B. ; Geraldis, Jaqueline C. ; Rogerio, Fabio ; Alvim, Marina K. M. ; Yasuda, Clarissa L. ; Ghizoni, Enrico ; Tedeschi, Helder ; Veiga, Diogo F. T. ; Henning, Barbara ; Souza, Welliton ; Rocha, Cristiane S. ; Vieira, Andre S. ; Dias, Elayne, V ; Carvalho, Benilton S. ; Gilioli, Rovilson ; Arul, Albert B. ; Robinson, Rena A. S. ; Cendes, Fernando ; Lopes-Cendes, Iscia

• Tipo de documento: Artigo Científico
• Fonte: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY; v. 9, n. 4, p. 14-pg., 2022-03-03.

Resumo

Objectives: We compared the proteomic signatures of the hippocampal lesion induced in three different animal models of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS): the systemic pilocarpine model (PILO), the intracerebroventricular kainic acid model (KA), and the perforant pathway stimulation model (PPS). Methods: We used shotgun proteomics to analyze the proteomes and find enriched biological pathways of the dorsal and ventral dentate gyrus (DG) isolated from the hippocampi of the three animal models. We also compared the proteomes obtained in the animal models to that from the DG of patients with pharmacoresistant MTLE+HS. Results: We found that each animal model presents specific profiles of proteomic changes. The PILO model showed responses predominantly related to neuronal excitatory imbalance. The KA model revealed alterations mainly in synaptic activity. The PPS model displayed abnormalities in metabolism and oxidative stress. We also identified common biological pathways enriched in all three models, such as inflammation and immune response, which were also observed in tissue from patients. However, none of the models could recapitulate the profile of molecular changes observed in tissue from patients. Significance: Our results indicate that each model has its own set of biological responses leading to epilepsy. Thus, it seems that only using a combination of the three models may one replicate more closely the mechanisms underlying MTLE+HS as seen in patients. (AU)

• Processo FAPESP: 16/19484-6 - Análise proteômica quantitativa de tecido neuronal obtido de pacientes e modelos animais de epilepsia
• Beneficiário: Barbara Henning Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07559-3 - Instituto Brasileiro de Neurociência e Neurotecnologia - BRAINN
• Beneficiário: Fernando Cendes
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/00213-0 - Análise metabolômica do plasma de pacientes com epilepsia do lobo temporal mesial: busca por biomarcadores de refratariedade medicamentosa
• Beneficiário: Alexandre Barcia de Godoi
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/12960-4 - Análise proteômica de tecido hipocampal obtido de pacientes e de modelos animais de Epilepsia do Lobo Temporal Mesial: um estudo comparativo
• Beneficiário: Amanda Morato Do Canto
• Modalidade de apoio: Bolsas no Brasil - Doutorado