Alterações de expressão gênica induzidas pela administração intracerebroventricular de estreptozotocina em curto e medio prazo

• Autor(a) principal: Silva, Henrique Gulin de Carvalho e
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório do Centro Universitário Braz Cubas
• Texto Completo: https://repositorio.cruzeirodosul.edu.br/handle/123456789/2286
• topic: Biotecnologia industrial; Doença de Alzheimer; Degenaração neural; Estreptozocina; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Streptozotocin (STZ) when administrated in low doses intracerebroventriculary (icv) in animals can cause very similar symptoms of those we see in Alzheimer Disease (AD), providing an animal model for the study of this dementia in conditions close to ideal. However, several variables influence the results obtained in research using this animal model. Time of exposure to the drug is one example of a variable that needs more in-depth studies for a standardization in this type of animal model. Thus, candidate genes based on known symptoms of Alzheimer's disease were chosen, such as neuroinflammation, oxidative stress, neuronal death and activation of microglia. Cx3cl1, and Il-1β are genes related to microglia activation, in which CX3CL1 and CX3CR1 are portrayed as factors of improvement in the neuroinflammatory status. While Gpx4 is related to oxidative stress. These genes were tested in two temporal contexts, with and without the administration of STZ in short-term (1 month) and medium-term (4 months). The total RNA from animal hippocampus were extracted and the analysis of the genes studied were done by the RT-qPCR technique. As a result, it was verified that gene expression variations for Il-1β appeared in group 1after the stz injection. In Gpx4 presented alterations on its expression, showing reduction on its expression levels only after 4 months of exposure. Cx3cl1 gene showed differences between the experimental groups euthanized after 1 month of STZ administration and the groups without the STZ application with one month and with four months. In conclusion, we found that there is a temporal effect connected to the differential expression of the studied genes, showing an increase of gene expression associated to neuroinflammation in the beginning of the neurodegenerative process, and a decrease in expression of genes associated to the control of oxidative stress.