Proteomics analysis of hippocampal tissue from patients and animal models of mesial temporal lobe epilepsy: a comparative study

Author(s)

Amanda Morato do Canto

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2020-07-07

Examining board members

Íscia Teresinha Lopes Cendes; Ljubica Tasic; Alexandre Leite Rodrigues de Oliveira; João Pereira Leite; Luciene Covolan

• Advisor: Íscia Teresinha Lopes Cendes; Andre Schwambach Vieira

Abstract

Epilepsy is a chronic neurological disorder resulting from changes in brain functions that affect approximately 2% of the world population. A feature common to all forms of epilepsy is the occurrence of epileptic seizures, abnormal neuronal discharges that occur in a transient, synchronous and disorganized manner, leading to clinical manifestations dependent on the brain region(s) affected. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, clinically characterized by epileptic seizures in the temporal lobe, many patients with TLE also present hippocampal sclerosis (HS). This typical histopathological lesion can be seen in patients and some animal models, characterizing mesial TLE (MTLE). The development and recent refinement of proteomics techniques offer powerful tools to find altered proteins in response to internal and external insults, changes in development, among other factors, many of which are involved in epilepsy. That said, this study aims to analyze and compare changes in protein levels that occur in the hippocampal tissue of patients and three animal models of MTLE. To refine the spatial resolution of the structures studied within the hippocampus, we used laser-microdissection to isolate specific regions and cell populations of interest. With that procedure, we generated the protein abundancy profile of 3 distinct animal models, the pilocarpine model, the kainic acid model, and the perforant pathways stimulation model. Our results indicate that, at the molecular level, each animal model has its specific features suggesting that the different insults generate epileptogenesis through different mechanisms. Furthermore, the models seem to recapitulate distinct aspects of the biological processes and pathways enriched in the patient tissue. We also performed specific studies with tissue from patients in different disease stages and characterized the abundancy of phosphorylated proteins. Our results of these two studies indicate that the molecular alterations in the patients changes with disease duration, suggesting a progression of the lesion in the medial temporal lobe structure. In conclusion, we believe that our study can provide crucial and original information regarding the molecular mechanisms involved in the hippocampal injury that occurs in MTLE (AU)

• FAPESP's process: 15/12960-4 - Proteomic analysis of hippocampal tissues obtained from patients and animal model of Mesial Temporal Lobe Epilepsy: a comparative study
• Grantee: Amanda Morato Do Canto
• Support Opportunities: Scholarships in Brazil - Doctorate