Proteomic evaluation of temporal lobe epilepsy in human and rat sujected to pilocarpine model, receiving or not neuroprotector agent R-PIA pretreatment

• Grant number: 08/00068-6
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): January 01, 2009
• Effective date (End): December 31, 2012
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Maria José da Silva Fernandes
• Grantee: Daniele Suzete Persike
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/50680-2 - Multimodal investigation of epileptogenesis with emphasis in the implementation of new animal models and new tools, AP.TEM

Abstract

The ELT is characterized by selective loss of neurons in the CA1 and CA3 subfields of the hippocampus, glial scar, dispersion in the dentate gyrus granule cells and mossy fiber sprouting. Studies to identify signaling pathways during epileptogenesis has shown that some routes involving both processes of neuronal death as neuroprotective agents, such as caspases. Caspases, Bim and Bax overexpression are considered pro-apoptotic, whereas Akt / PKB, Bcl-XL, calbindin and HSP 70 are anti-apoptotic molecules. Adenosine is a nucleoside that exerts anticonvulsant and neuroprotective, primarily through activation of A1 receptors. Its analogues may cause apoptosis or protect from cell death, by mechanisms still poorly understood. Previous studies in the pilocarpine model show that pretreatment with R-PIA reduces hippocampal neuronal death. Current studies have sought to identify molecules involved in the process of lesions present in the epileptic human tissue, and its expression in ELT model induced by pilocarpine with and without pretreatment with R-PIA. The objectives of this study are: 1) by proteomic analysis to investigate the proteins expressed in the hippocampus of TLE patients as well as in the hippocampus of rats submitted to pilocarpine model studied in the acute phase, latent and chronic; 2) determine the expression profile of these proteins by pre-treatment with R-PIA, 3) measure by Western blotting, and Bim Akt/Bcl-XL/HSP-70 / Bax / caspases in the hippocampus of rats treated with pilocarpine with or without R-PIA. Our interest is to understand the balance between pro and anti-apoptotic in ELT, and verify that the neuroprotective agent R-PIA is able to modulate some of these mechanisms.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PERSIKE, DANIELE SUZETE; MARQUES-CARNEIRO, JOSE EDUARDO; DE LIMA STEIN, MARIANA LEAO; TARGAS YACUBIAN, ELZA MARCIA; CENTENO, RICARDO; CANZIAN, MAURO; DA SILVA FERNANDES, MARIA JOSE. Altered Proteins in the Hippocampus of Patients with Mesial Temporal Lobe Epilepsy. PHARMACEUTICALS, v. 11, n. 4 DEC 2018. Web of Science Citations: 3.