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Role of mitochondrial oxidative stress and UCP2 in epilepsy experimental model induced by pilocarpine

Grant number: 13/24515-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2014
Effective date (End): March 31, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Fulvio Alexandre Scorza
Grantee:Mariana Bocca Nejm Abou Haidar
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in humans. Evidence supports the fact that neuronal injury observed in epilepsy may be the result of an overproduction of free radicals (oxidative stress) and related to excitotoxicity event. Mitochondria is responsible for ATP synthesis but also is involved in Ca2+ uptake and release, transient mitochondrial permeability and in ROS (reactive oxygen species) generation. It is known that excessive ROS generation can promote ultrastructural changes in the respiratory chain. The first uncoupling protein mitochondrial of respiratory chain (UCP, uncoupling mitochondrial protein) described was UCP1 and others subsequentlywere discovered. The UCP2 is significantly expressed in certain regions in the brain and is responsible for stabilizing the mitochondrial membrane potential, an important event suggested to reduce cell death. It is suggested that activation of UCP2 may protect neurons in degenerative processes associated with oxidative stress and mitochondrial changes in potential trasmembrana so, may be therefore, neuroprotective for the brain. In the first stage of the project we aim to evaluate on the 3 periods of pilocarpine model: the protein expression of UCP2 and antioxidant enzymes (MnSOD and GPx) in hippocampus mitocondria, the enzymatic activity of respiratory chain complexes, the production of ROS and the morphology of these mitochondrias. In the second stage using UCP2 siRNA injected 48 hours before pilocarpine, we aim to investigate the relationship between UCP2 and free radical production. We intend to observe, using UCP2 siRNA, possible phenotypic changes during the course of the experimental model, analyze the neuronal death, the morphology of these mitochondria, the ROS production and enzymatic activity of respiratory chain complexes. We inted that the expected results acts as basis for understanding the role of mitochondrial oxidative stress and the involvement of UCP2 in epileptogenesis and on its progression by providing knowledge for further studies and therapeutic advances.