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In vitro characterization of medial ganglionic eminence neuronal precursors followed by in vivo evaluation of their anticonvulsant potencial after transplantation in epileptic animals

Grant number: 11/19686-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2012
Effective date (End): February 29, 2016
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Beatriz de Oliveira Monteiro
Grantee:Simone Amaro Alves Romariz Bertola
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

In epilepsy, spontaneous recurrent seizures develop from neuronal alterations in certain areas of the central nervous system. Continuous neuronal firing and high frequency can be generated by a surrounding inhibitory synaptic dysfunction. Therefore, the consequences of the loss or dysfunction of GABAergic interneurons are critical for the development of epileptic condition. The inhibitory interneurons are originated in the brain regions of the telencephalon known as the caudal and medial ganglionic eminences (MGE). MGE precursor cells have the ability to migrate and differentiate into GABAergic inhibitory interneurons, modifying the inhibitory tone when transplanted into a host brain. Therefore, transplantation of precursor cells derived from the MGE of E14 embryos could modify the neuronal circuitry in neurological disorders in which the inhibitory function is altered, as in epilepsy. The objective of this project is to characterize the neuronal precursor cells derived from the E14 MGE in vitro and verify their anticonvulsant potential in vivo by transplantation into adult animals during the epileptogenic phase and evaluating their effects on chronic seizures. The in vitro study aims to investigate whether changes in culture conditions can alter the pattern of differentiation into inhibitory neurons. Transplantation in vivo was designed to confirm the conditions found in vitro and strengthen the GABAergic inhibitory function in the epileptic brain.