Streptozotocin-induced neurodegeration in wistar rats: short and long term effects on behavior and brain gene expression

• Autor(a) principal: Pfutzenreuter, Gabrielle
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório do Centro Universitário Braz Cubas
• Texto Completo: https://repositorio.cruzeirodosul.edu.br/handle/123456789/2256
• topic: Biotecnologia; Alzheimer disease; Memory disorders; Anxiety; Hippocampus; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Alzheimer's disease (AD) is the most common type of dementia in humans, characterized by the accumulation of misfolded proteins in the brain, which leads to oxidative damage, inflammation and synaptic dysfunction. In order to study the disease, several animal models have been tested, including a nontransgenic rat model based on intracerebroventricular (icv) injection of Streptozotocin (STZ). Although widely used, there is a lack of information about the possible association between the cognitive decline and molecular changes generated when the animal is exposed to STZ for a long period. This study evaluated the short and long-term memory functions, anxiety, motor activity and decision make of the icv STZ rat model by of behavioral approaches. Additionally, gene expression of 5 AD related genes was analyzed by molecular tools. Thirty-two male Wistar rats were divided equally among 4 groups: one group which received icv STZ and one control group which received vehicle, for the short memory function evaluation (euthanized 1 month after the administration of the STZ - Phase 1), one group which received icv STZ and one control group which received vehicle for the long-term memory function evaluation (euthanized 4 months after the administration of the STZ - Phase 2). To evaluate behavioral functions, animals were exposed to the elevated plusmaze. The behavioral tests were followed by brain removal, hippocampal dissection, RNA extraction and qRT-PCR to assess the expression levels of Apoe, C3, Ps-1, Mapt and Atf4. Analyzes demonstrated that rats that received icv-STZ showed impairments in behavior functions, as anxiety, memory and risk assessment, Additionally, C3, which has an important role in inflammation, showed an increased expression one month after drug administration, indicating the presence of an key inflammatory process related to the degenerative events on hippocampal formation.