Navegando por Palavras-chave "Neurônio motor"

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    Aplicação de terapias celulares em um modelo experimental de esclerose lateral amiotrófica
    (Universidade Federal de São Paulo (UNIFESP), 2011-11-24) Barnabé, Gabriela Filoso [UNIFESP]; Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons, to which no efficient treatment is currently available able of increasing life span. Because ALS is a multifactorial disease, it is supposed that the most promising therapies may be the ones capable of playing multiple roles. Despite some aspects remained unknown, stem cells (SC) may be able to modify the lesion microenvironment, modulating multiple systems and, under this aspect, they show up as candidates for neurodegenerative disease therapies. In this work we used a model of transgenic rats that superexpress a mutaded form of human superoxide dismutase I (SOD1) as a tool to study ALS. In the first step of this work we revealed some of the cellular and molecular events that took place during the neuronal degeneration process in ALS rat model. We noticed that motor neuron death was accompanied by gliosis, increased expression of inflammatory cytokines and some growth factors, besides the mobilization of endogenous neural precursor cells. Accordingly to the data acquired in the first step, two disease stages were chosen to study cell therapy in SOD1 rats: the pre-symptomatic stage and the initial symptomatic stage. The second step experimental design has been organized accordingly to two distinct questions: I) Can SC therapies retard disease progression? II) How SC behave to neurodegenerative environment in different stages? The effects of various types of SC were compared: neural, mesenchymal and the combination of both. SC transplantation did not promoted any motor function improvement, possibly due to the great variability of ALS rat model and to the fact that SC did not went far from the transplantation site. Each type of SC used here resulted in distinct effects over ALS degenerative microenvironment, highlighting gliosis modulation, mobilization of endogenous neural precursors and differential expression of chemokines and cytokines in the spinal cord. These effects depends on disease stage when cell transplantation happened, illustrating a complex interaction between donor and host cells. Finally, neurospheres derived from SOD1 transgenic fetal spinal cord, that consists in an ALS in vitro study model, indicated that some alterations promoted by mutated SOD1 can be early noticed in the development. A main contribution of this work is in the conception that the development of cell therapies for ALS must consider a large comprehension of the degenerative mechanisms and the biological properties of the several sources of SC.