Epileptogenesis in transgenic mice with tonin overexpression in the brain: study in pilocarpine model of epilepsy

Abstract

The renin-angiotensin system (RAS) has been well documented is associated with several vital functions. Brain RAS has been related to neurodegenerative diseases only in the last years. Recently, our group showed, for the first time, the association between angiotensin II (Ang II) receptors AT1 and AT2 and human temporal lobe epilepsy (TLE). We observed an overexpression of AT1 and AT2 receptors in the hippocampus of TLE patients with hippocampal sclerosis, showing an important correlation between RAS and neurodegenerative process related to epilepsy. Thus, aim of this study will to investigate of RAS during epileptogenic process. This project will be developed in transgenic mice presenting overexpression of tonin in the brain. This enzyme is a serine protease that converts AngII from AngI or directly from angiotensinogen. Thus, with this approach will be possible to better understand the real function of AngII into epileptogenic process. Transgenic and control mice will be submitted to pilocarpine-induced epilepsy, that mimics human TLE. These animals will be also evaluated in behavioral parameters such as seizure susceptibility, duration of silent phase, seizure frequency in chronic phase, cell death pattern and mossy fiber sprouting. Inflammatory mediators will be also analyzed in the hippocampus. This study could provide perspectives related to AngII function during epileptogenesis, supporting future therapeutic targets. (AU)