Dimetil Fumarato exerce efeito neuroprotetor contra dano oxidativo e comportamental em um modelo experimental de autismo induzido por LPS no DG9,5
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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
Borges, Lidiane Pinto
Orientador
Fortunato, Jucélia Jeremias
Coorientador
Resumo
O Transtorno do Espectro Autista (TEA) é um conjunto de condições heterogêneas do desenvolvimento neurológico que se caracteriza por apresentar dificuldades em comunicação social e restrita, como também comportamentos repetitivos e sem interesses. Nos últimos anos a prevalência do TEA tem aumentado em todo o mundo, estima-se que haja 1 caso para cada 68 crianças nascidas. Existem hipóteses de que o TEA seja causado por alterações neuroimunes que possam estar relacionadas com as diferentes manifestações clínicas apresentadas por este transtorno. A proposta deste estudo é considerar a neuroinflamação como hipótese etiológica do TEA e a partir daí, sugerir uma terapia que envolva o bloqueio da liberação das citocinas pró-inflamatórias através do controle da infecção materna ou a diminuição da ativação da micróglia por meio do tratamento com Dimetil Fumarato (DMF). O estudo teve como objetivo avaliar os efeitos de diferentes doses de DMF sobre parâmetros bioquímicos e comportamentais de ratos Wistar submetidos à um modelo experimental de TEA. Os animais foram distribuídos em seis grupos experimentais, de acordo com a exposição pré-natal ao lipopolissacarídeo (LPS) e à dose administrada de DMF iniciou-se em (PND) 30, e seguiu por 14 dias consecutivos, administrado duas vezes ao dia, intraperitonealmente, nas doses de 5 e 15 mg/kg, conforme grupo experimental. Os resultados deste estudo sugerem que a ativação imune materna causou na prole alterações comportamentais e neuroquímicas condizentes com o TEA, e o tratamento com DMF proporcionou resultados positivos, tanto comportamentais como neuroquímicos.
The Autism Spectrum Disorder (ASD) is a set of heterogeneous neurodevelopmental conditions characterized by presenting difficulties in social and restricted communication, as well as repetitive and without interest behaviors. In recent years, the prevalence of ASD has increased worldwide, it is estimated there is 1 case per 68 children born. There are chances that the ASD is caused by neuroimmunes changes that might be related to the different clinical manifestations of this disorder. The purpose of this study is to consider the neuroinflammation as an etiological hypothesis of the ASD and from there, suggest a therapy that involves blocking the release of proinflammatory cytokines by controlling the maternal infection or decrease the activation of microglia by treating with Dimethyl Fumarate (DMF). The study aimed to evaluate the effects of different doses of DMF on biochemical and behavioral parameters of Wistar rats submitted to an experimental model of ASD. The animals were distributed in six experimental groups, according to prenatal exposure to lipopolysaccharide (LPS) and administered dose of DMF began in (PND) 30, and continued for 14 consecutive days, administered twice daily, intraperitoneally at doses of 5 and 15 mg/kg, according to experimental group. The results of this study suggest that maternal immune activation caused behavioral and neurochemical changes in the offspring consistent with the ASD, and treatment with DMF yielded positive results, both behavioral and neurochemical.
The Autism Spectrum Disorder (ASD) is a set of heterogeneous neurodevelopmental conditions characterized by presenting difficulties in social and restricted communication, as well as repetitive and without interest behaviors. In recent years, the prevalence of ASD has increased worldwide, it is estimated there is 1 case per 68 children born. There are chances that the ASD is caused by neuroimmunes changes that might be related to the different clinical manifestations of this disorder. The purpose of this study is to consider the neuroinflammation as an etiological hypothesis of the ASD and from there, suggest a therapy that involves blocking the release of proinflammatory cytokines by controlling the maternal infection or decrease the activation of microglia by treating with Dimethyl Fumarate (DMF). The study aimed to evaluate the effects of different doses of DMF on biochemical and behavioral parameters of Wistar rats submitted to an experimental model of ASD. The animals were distributed in six experimental groups, according to prenatal exposure to lipopolysaccharide (LPS) and administered dose of DMF began in (PND) 30, and continued for 14 consecutive days, administered twice daily, intraperitoneally at doses of 5 and 15 mg/kg, according to experimental group. The results of this study suggest that maternal immune activation caused behavioral and neurochemical changes in the offspring consistent with the ASD, and treatment with DMF yielded positive results, both behavioral and neurochemical.
Palavras-chave
Autismo, Estresse oxidativo, Sistema nervoso - Doenças