Inflamação hipocampal em dois modelos animais de resistência à insulina: ratos Wistar obesos por dieta obesogênica e ratos Goto-Kakizaki diabéticos tipo 2 magros

• Ano de defesa: 2021
• Autor(a) principal: Oliveira, Vivian Araújo Barbosa de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Cruzeiro do Sul; Brasil; Programa de Pós Graduação em Ciências da Saúde; Cruzeiro do Sul
• Palavras-chave em Português: Diabetes Mellitus tipo 2; Hiperglicemia; Hipocampo; Distúrbios cognitivos; Neuroinflamação; CNPQ::CIENCIAS DA SAUDE
• Link de acesso: https://repositorio.cruzeirodosul.edu.br/handle/123456789/4103

The chronic hyperglycemic state that progresses to peripheral insulin resistance (IR) is associated with brain inflammation and the development of cognitive disorders, but the mechanisms of this interaction remain unclear. In the present study, we evaluated the effects of IR on hippocampal inflammation, the brain region most associated with cognitive function, in a spontaneous model of type 2 diabetes mellitus (DM2) by genetic factors in Goto-Kakizaki rats or induced by an obesogenic diet in Wistar rats. Male rats with 120-day-old were divided into three groups: Wistar fed a balanced diet (BA), Wistar fed a high fat and high sugar diet (GA) and Goto Kakizaki (GK) rats fed a BA diet for eight weeks. Body mass and food consumption were evaluated, with glucose and insulin tolerance tests in the seventh week of the diet. It was analyzed the gene expression of inflammatory mediators (TNF-α, IL-6, IL 1β and NOS1) and brain proteins (Tau, beta-amyloid and BDNF) in the hippocampus by real-time polymerase chain reaction (qPCR). Protein expression of inflammatory mediators (TNF-α, IL-1β, p-p65-NFkB and leptin receptor) and brain proteins (p-Tau and beta-amyloid) was determined in the hippocampus by Western blot. The GA group showed increased body mass gain and caloric consumption, fasting hyperglycemia and insulin intolerance, without significant changes in the hippocampus, compared to BA. The GK rats demonstrated fasting hyperglycemia, glucose and insulin intolerance, and hippocampal changes: increased IL-6, IL-1β and BDNF gene expression, decreased NOS-1 expression, increased p-p65-NF-κB and IL-1β protein, TNF-α and BIM protein reduction and increased leptin receptor in the hippocampus and plasma leptin. The chronic state of hyperglycemia and genetic DM2 in 120-days-old GK animals would be determinant in hippocampal inflammation compared to hyperglycemic and insulin-intolerant Wistar animals induced by an eight-week obesogenic diet.