Participação da via de sinalização WNT/β-catenina na desdiferenciação de astrócitos e resposta à lesão cerebral

• Ano de defesa: 2017
• Autor(a) principal: Pinto, Agnes Araujo Sardinha [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Traumatic injury; Regeneration; Astrocyte reality; Ascites; Cellular dedifferentiation; Lesão traumática; Regeneração; Realividade astrocitária; Aslrócitos; Desdiferenciação celular
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5209961; http://repositorio.unifesp.br/handle/11600/50527

Neurogenesis in the central nervous system (CNS) of adult mammals occurs mainly in two restricted and specialized regions of the brain, the subgranular and the subventricular zone. In addition to physiological neurogenesis, there are also stimulating the production of new neural cells in response to a brain injury. The astrocytes also play an important role in the organism's response to lesions in the CNS, participating in the determination of the cellular proliferative activity in the neurogenic regions. Another response of these cells is the of cellular activation, where there may be a transition from a subpopulation of astrocytes to a less differentiated state. This transition is characterized by changes in phenotype and entry into a proliferative state suggesting the occurrence of dedifferentiation, in which the asth- neural stem cell characteristics. Little is known about the functions reactive astrocytes can perform, their effects on the other cells of the CNS and their contribution to tissue regeneration. Therefore, the investigation of the factors involved in the process of astrocyte activation becomes relevant in the sense of " identify possible therapeutic targets to optimize the generation of new cells multipotent at the site of the injury, which would allow obstacles to be and cell migration from the neurogenic niches. Given the importance of elucidate the pathways involved in astrocytic activation, this study sought to investigate the possible participation of the Wntll3-catenin signaling pathway in this process. For Therefore, we subjected astrocytes in primary culture to the model of mechanical vitro and to treatment with Wnt 3a protein or its inhibitor (Dickkopf-1). As a result, treatment with the pathway inhibitor reduced the ability to of astrocyte derived neurospheres. In the in vivo model, we also observed increased expression of Wnt 3a three days after injury. However, inhibition of the in this same animal model did not cause changes in behavior proliferation and expression of astrocyte activation markers. Considering the results presented here, we conclude that the WntII-catenin pathway is required, but not sufficient, to induce the acquisition of stem cell phenotype by reactive astrocytes, suggesting that other factors, not studied in this work, are necessary for the process to take place.