Avaliação da integridade da barreira hematoencefálica e a atividade das metaloproteinases de matriz 2 e 9 em camundongos com distrofia muscular congênita 1D
Carregando...
Arquivos
Data
2015
Tipo de documento
Dissertação
Título da Revista
ISSN da Revista
Título de Volume
Área do conhecimento
Ciências da Saúde
Modalidade de acesso
Acesso aberto
Editora
Autores
Silva, Aryadnne Luyse Schactae da
Orientador
Comim, Clarissa Martinelli
Coorientador
Resumo
Distrofia Muscular Congênita do tipo 1D é uma doença neuromuscular, caracterizada pela glicosilação anormal da proteína alfa-distroglicana, e isto pode estar fortemente implicada no desenvolvimento anormal do sistema nervoso central, levando ao comprometimento cognitivo observado em pacientes e em modelo animal. A fisiopatologia do envolvimento do cérebro ainda não está clara, entretanto, pesquisas recentes indicam uma possível ligação entre alterações do sistema nervoso central com quebra da integridade da barreia hematoencefálica. A barreira é uma estrutura presente entre o tecido encefálico e circulatório, constituído por metaloproteinases de matriz, que possuem a função de controlar e regular a homeostase do sistema nervoso central. Neste contexto, o objetivo deste estudo foi avaliar a integridade da barreira hematoencefálica e a atividade das metaloproteinases de matriz 2 e 9 em tecido encefálico no animal Large. Para o estudo, usaram-se camundongos machos adultos (60 dias de vida), homozigotos (animais Large), heterozigotos e selvagens (C57BL/6) para a avaliação da integridade da barreira hematoencefálica e a atividade das metaloproteinases 2 e 9 em hipocampo, estriado e córtex cererbral, a escolha das estruturas avaliadas foi devido a estas apresentarem barreira hematoencefálica segundo estudos prévios. Verificou-se um aumento da permeabilidade da barreira hematoencefálica significativo nas estruturas de hipocampo e estriado em camundongos Large homozigotos em comparação com o grupo selvagem. Em relação as metalopreteinases, houve um aumento da atividade da metalopreoteinase 2 nas estruturas de córtex e estriado, quanto a metaloproteinase 9 houve um aumento na sua atividade na estrutura hipocampo quando comparados ao grupo selvagem. Este estudo mostrou a evidência de que uma glicosilação anormal da proteína alfa-distroglicana pode estar afetando a permeabilidade da barreira hematoencefálica e da atividade das metaloproteinases 2 e 9 no tecido encefálico, contribuindo para o envolvimento do sistema nervoso central na distrofia muscular congênita do tipo 1D.
Congenital muscular dystrophy type 1D is a neuromuscular disease characterized by abnormal glycosylation of alpha-dystroglycan protein, and that may be closely involved in the abnormal development of the central nervous system, leading to cognitive impairment observed in patients and in animal model. The pathophysiology of brain involvement is still unclear, however, recent research indicates a possible link between changes in the central nervous system with breaking the integrity of the blood brain barrier. The barrier structure is present between the circulatory and brain tissue, consisting of matrix metalloproteinases, which have the function of controlling and regulating the homeostasis of the central nervous system. In this context, the aim of this study was to evaluate the integrity of the blood brain barrier and the activity of matrix metalloproteinases 2 and 9 in brain tissue in Large animal. For the study, it was used adult male mice (60 days old), homozygous (Large animals), heterozygous and wild (C57BL / 6) for evaluating the integrity of the blood brain barrier and the activity of metalloproteinases 2 and 9 in the hippocampus, striatum and cortex. There was a significant increase in permeability of the blood brain barrier in hippocampal structures in Large homozygous mice compared with wild group. Regarding the metalloproteinases, there was an increase in metalloproteinase 2 activity in cortex structures and striatum, as the metalloproteinase 9 there was an increase in activity in the hippocampus structure when compared to the wild group. This study showed evidence that an abnormal glycosylation of alpha-dystroglycan protein may be affecting the permeability of the blood-brain barrier and the activity of metalloproteinases 2 and 9 in brain tissue, thus contributing to the involvement of the central nervous system in congenital muscular dystrophy type 1D.
Congenital muscular dystrophy type 1D is a neuromuscular disease characterized by abnormal glycosylation of alpha-dystroglycan protein, and that may be closely involved in the abnormal development of the central nervous system, leading to cognitive impairment observed in patients and in animal model. The pathophysiology of brain involvement is still unclear, however, recent research indicates a possible link between changes in the central nervous system with breaking the integrity of the blood brain barrier. The barrier structure is present between the circulatory and brain tissue, consisting of matrix metalloproteinases, which have the function of controlling and regulating the homeostasis of the central nervous system. In this context, the aim of this study was to evaluate the integrity of the blood brain barrier and the activity of matrix metalloproteinases 2 and 9 in brain tissue in Large animal. For the study, it was used adult male mice (60 days old), homozygous (Large animals), heterozygous and wild (C57BL / 6) for evaluating the integrity of the blood brain barrier and the activity of metalloproteinases 2 and 9 in the hippocampus, striatum and cortex. There was a significant increase in permeability of the blood brain barrier in hippocampal structures in Large homozygous mice compared with wild group. Regarding the metalloproteinases, there was an increase in metalloproteinase 2 activity in cortex structures and striatum, as the metalloproteinase 9 there was an increase in activity in the hippocampus structure when compared to the wild group. This study showed evidence that an abnormal glycosylation of alpha-dystroglycan protein may be affecting the permeability of the blood-brain barrier and the activity of metalloproteinases 2 and 9 in brain tissue, thus contributing to the involvement of the central nervous system in congenital muscular dystrophy type 1D.
Palavras-chave
Doenças neuromusculares, Distrofia muscular, Sistema nervoso central