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New approaches of studies on neural stem cells in central nervous system diseases

Abstract

Neural stem cells (CTN) are multipotents cells and capable of self-renewal, proliferation and generation of specific cell populations such as neurons, astrocytes and oligodendrocytes. The development of protocols for expansion and differentiation in vitro and transplantation in vivo favored the emergence of new perspectives for the use of these cells in incurable diseases, such as Alzheimer's Disease (DA), and others for which there is still no effective pharmacological treatment, such as epilepsy.In this scenario, changes in cell culture conditions and vectors insertion in CTN for gene therapy could be promising alternatives for treatment of these pathologies. Modifications of factors and conditions in CTN culture in vitro could lead to a greater amount of inhibitory interneurons, and consequently a replacement of GABAergic interneurons when transplanted into the hippocampus, diminishing epileptic seizures by decreasing the hyperexcitability. In addition, CTN, separately or overexpressing NGF (Nerve Growth Factor), transplanted into the hippocampus of double transgenic animals for DA (2xTg-DA), could contribute to the neural regeneration and decrease of A² deposition and senile plaques through stabilization of NGF brain levels. In this project, we propose to investigate the therapeutic potential of CTN in vitro directed to produce an enriched population of inhibitory interneurons, and the hippocampal transplantation of CTN in epileptic animals. Moreover, we will investigate the benefits of CTN transplantation on the cognitive functions and neuronal regeneration and the effect of NGF overexpression in decreasing senile plaques in 2xTg-DA model. (AU)

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