Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling.

Vascular endothelial growth factor (VEGF) regulates angio/neurogenesis and also tightly links to the pathogenesis of Alzheimer's disease (AD). Although exercise has a beneficial effect on neurovascular function and cognitive function, the direct effect of exercise on VEGF-related signaling and cognitive deficit in AD is incompletely understood. Therefore, the purpose of this study was to investigate the protective effect of exercise on angiostatin/VEGF cascade and cognitive function in AD model rats. Wistar male rats were randomly divided into five groups: control (CON), injection of DMSO (Sham-CON), CON-exercise (sham-EX), intrahippocampal injection of Aß (Aß), and Aß-exercise (Aß-EX). Rats in EX groups underwent treadmill exercise for 4 weeks, then the cognitive function was measured by the Morris Water Maze (MWM) test. mRNA levels of hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and angiostatin were determined in hippocampus by RT-PCR. We found that spatial learning and memory were impaired in Aß-injected rats, but exercise training improved it. Moreover, exercise training increased the reduced mRNA expression level of VEGF signaling, including HIF1α, VEGF, and VEGFR2 in the hippocampus from Aß-injected rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from Aß-injected rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in Aß-injected rats, possibly through enhancing VEGF signaling and reducing angiostatin.

Exercise-induced changes of MCT1 in cardiac and skeletal muscles of diabetic rats induced by high-fat diet and STZ

We hypothesized that a part of therapeutic effects of endurance training on insulin resistance is mediated by increase in cardiac and skeletal muscle mitochondrial lactate transporter, monocarboxylate transporter 1 (MCT1). Therefore, we examined the effect of 7 weeks endurance training on the mRNA and protein expression of MCT1 and MCT4 and their chaperon, CD147, on both sarcolemmal and mitochondrial membrane, separately, in healthy and type 2 diabetic rats. Diabetes was induced by injection of low dose of streptozotocin and feeding with high-fat diet. Insulin resistance was confirmed by homeostasis model assessment-estimated insulin resistance index and accuracy of two membranes separation was confirmed by negative control markers (glucose transporter 1 and cytochrome c oxidase. Real-time PCR and western blotting were used for mRNA and protein expression, respectively. Diabetes dramatically reduced MCT1 and MCT4 mRNA and their expression on sarcolemmal membrane whereas the reduction in MCT1 expression was less in mitochondrial membrane. Training increased the MCT1 mRNA and protein expression in both membranes and decreased insulin resistance as an adaptive consequence. In both tissues increase in CD147 mRNA was only parallel to MCT1 expression. The response of MCT1 on sarcolemmal and mitochondrial membranes was different between cardiac and skeletal muscles which indicate that intracellular lactate kinetic is tissue specific that allows a tissue to coordinate whole organism metabolism (AU)

Exercise-induced changes of MCT1 in cardiac and skeletal muscles of diabetic rats induced by high-fat diet and STZ.

We hypothesized that a part of therapeutic effects of endurance training on insulin resistance is mediated by increase in cardiac and skeletal muscle mitochondrial lactate transporter, monocarboxylate transporter 1 (MCT1). Therefore, we examined the effect of 7 weeks endurance training on the mRNA and protein expression of MCT1 and MCT4 and their chaperon, CD147, on both sarcolemmal and mitochondrial membrane, separately, in healthy and type 2 diabetic rats. Diabetes was induced by injection of low dose of streptozotocin and feeding with high-fat diet. Insulin resistance was confirmed by homeostasis model assessment-estimated insulin resistance index and accuracy of two membranes separation was confirmed by negative control markers (glucose transporter 1 and cytochrome c oxidase. Real-time PCR and western blotting were used for mRNA and protein expression, respectively. Diabetes dramatically reduced MCT1 and MCT4 mRNA and their expression on sarcolemmal membrane whereas the reduction in MCT1 expression was less in mitochondrial membrane. Training increased the MCT1 mRNA and protein expression in both membranes and decreased insulin resistance as an adaptive consequence. In both tissues increase in CD147 mRNA was only parallel to MCT1 expression. The response of MCT1 on sarcolemmal and mitochondrial membranes was different between cardiac and skeletal muscles which indicate that intracellular lactate kinetic is tissue specific that allows a tissue to coordinate whole organism metabolism.