Aumento dos níveis do substrato do receptor de insulina e da distribuição do receptor de glutamato fosforilado na serina 845 no hipocampo de ratos machos adultos programados por um modelo de malnutrição materna

• Autor(a) principal: Barbosa, Ana Carolina Bastos
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12808
• topic: 0% Protein Diet; Central nervous system development; Metabolic programming; Memory; Dieta 0% Proteína; Desenvolvimento do sistema nervoso central; Programação metabólica; Memória; Desnutrição proteica; Óxido nítrico sintase; Desenvolvimento cognitivo; Lactação; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Physiological and metabolic changes that occur in intrauterine or early postnatal life, elicited by an external factor and that have repercussions in adult life can be defined as metabolic programming. Protein malnutrition in early stages of life can cause effects during development and in adult life, such as changes in glucose homeostasis, imbalance in insulin and glucocorticoid secretion, increased insulin sensitivity, and increased leptin response. In a model of malnutrition in rats, with administration of 0% protein to damns during the first 10 lactation days, we have demonstrated a delay in neuropeptide Y (NPY) distribution in the hypothalamus and in the hippocampus, alterations in the pattern of nitric oxide synthase (ONS) distribution in adult life, as also changes in learning and memory. The objective of this study was to investigate whether Wistar rats submitted to this model of protein malnutrition present alterations in insulin receptor substrate 1 (IRS1) levels and in the distribution of the phosphorylated glutamate receptor subunit 1 (Glur-1) at serine 845 in the hippocampus. From the first day of lactation, nursing rats had their litters adjusted to six males and were separated into three groups: control (GC), malnutrition (GM) and pair-fed (GPF). Malnutrition occurred through administration to the damns of a 0% protein diet and a caloric restriction group was performed by administering 12 grams of commercial chow per day to the GPF mother. The GC received commercial chow (22% protein). Food intake and body mass of offspring were measured during development. IRS1 levels were quantified in the hippocampus of offspring at P10 and P60. The distributions of pGlur-1 (Ser 845) and NeuN positive cells were also evaluated in the hippocampus in P10 and P60. The GM offspring had lower body mass in relation to the GC from P4 to P60, except for P30. GPF also has a reduction in body mass compared to controls. No quantitative differences were found for IRS-1, NeuN and pGlur-1 at P10. In P60, GM presented higher levels of IRS1 in the hippocampus and greater distribution of pGlur-1 in CA3, in relation to the control group. No change was observed in the total number of neurons. It was concluded that protein restriction during lactation affected the body mass development of the offspring, but did not cause immediate impacts on the IRS1 and pGlur-1 molecules in the hippocampus. The results observed at P60, with increased IRS1 and pGlur-1 levels suggest that these animals undergo metabolic programming, impairing insulin signaling and increasing insulin receptor substrate in the hippocampus, followed by an increase in the number of Glur-1 phosphorylated at serine 845. We can also suggest that these results corroborate previous studies of our group that observed an improvement in spatial memory and exploratory activity in this model.