Effects of physical exercise on the insulin signaling and neuronal survival in GLUT4 KO mice

Abstract

A few metabolic parameters require accurate and rigid as glycemic control regulation. Changes in serum glucose concentrations trigger many systemic responses that can lead to the onset of diabetes mellitus (DM). The DM in turn, has been associated with the development of cognitive impairment, neurodegeneration and Alzheimer's disease (AD). Recent studies reveal the importance of the physical exercise as prevention and treatment of various neurological disorders. Thus, the aim of this study is to investigate the effects of moderate exercise on insulin signaling pathway, cell survival factors and proteins related to apoptosis in the hippocampus of Hyperinsulinemic / Hyperglycemic mice. Fifity C57L/J GLUT4+/- Hyperinsulinemic/hyperglycemic (HH) adult mice (180 day old) will be used in this research. The animals will be randomly assigned into three groups according to the genotype and exercise protocol: Sedentary Control (Wt), GLUT4+/- HH Sedentary (GS), GLUT4+/- HH Exercised (GE). The exercise protocol consisted of thirty minutes swimming exercise at the Maximal Lactate Steady State (MLSS) workload for three consecutive days. The animals will be submitted to a cognitive test (Morris maze) and then euthanized to collect blood samples for blood glucose, cholesterol , triglycerides and free fatty acids determination . Furthermore , the hippocampus will be extirpated to determine the expression of proteins involved in cell survival, through the insulin action (PI3K, Akt, ERK1/2) and apoptosis ( FoxO1 , FOXO3a MKP -3 , TRAIL, BCL-2 , FasL, Caspase-3, Caspase-6, Caspase-9). Such analyzes will be performed by immunoprecipitation and immunoblotting . At the end of the experiment, we expected to elucidate the main changes caused by hyperinsulinemia and hyperglycemia in steps that precede the onset of neurodegeneration in the hippocampus and the role of exercise in preventing possible failures in the central nervous system. (AU)