The effects of muscular dystrophy, exercise and sActRIIB-Fc on molecular signature of skeletal muscle in mice
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ABSTRACT: To study the combined effect of myostatin/activin inhibition and exercise on muscle mass and pathophysiology, young mdx mice, a model for Duchenne Muscular Dystrophy, were injected with soluble activin receptor-Fc (sActRIIB-Fc) or placebo (PBS) 1x/week for a 7-week period, in combination with or without voluntary running. C57Bl/10ScSnJ mice injected with PBS acted as wildtype controls. Microarray expression analysis from skeletal muscle was performed using m. gastrocnemies as the sample. We found thatexercise or a combination of exercise and sActRIIB-Fc treatment is more effective in correcting gene expression profiles of dystrophic muscles than the sActRIIB-Fc treatment alone. We also identified several pathways and proteins that were affected by exercise and sActRIIB-Fc together or independently. Total RNA obtained from gastrocnemius muscle of mdx mice divided into four groups: 1) control (injected with PBS, n=5), 2) runners (voluntary wheel running for 7 weeks, injected with PBS, n=5), 3) sActRIIB-Fc -treated (n=5), and 4) runners with sActRIIB-Fc-treatment (n=5). sActRIIB-Fc or PBS was injected intraperitoneally once a week with a 5-mg/kg dose of sActRIIB-Fc. In addition, wildtype mice served as healthy controls (n=4).
Project description:To study the combined effect of myostatin/activin inhibition and exercise on muscle mass and pathophysiology, young mdx mice, a model for Duchenne Muscular Dystrophy, were injected with soluble activin receptor-Fc (sActRIIB-Fc) or placebo (PBS) 1x/week for a 7-week period, in combination with or without voluntary running. C57Bl/10ScSnJ mice injected with PBS acted as wildtype controls. Microarray expression analysis from skeletal muscle was performed using m. gastrocnemies as the sample. We found thatexercise or a combination of exercise and sActRIIB-Fc treatment is more effective in correcting gene expression profiles of dystrophic muscles than the sActRIIB-Fc treatment alone. We also identified several pathways and proteins that were affected by exercise and sActRIIB-Fc together or independently.
Project description:This experiment was designed to identify changes in gene expression in the brain (specifically the hipocampus) in relation to variable levels of voluntary exercise. Male C57Bl/6J mice were weaned onto a low fat diet (LF; Research Diets D12329, 11% kcal fat) and given continuous access to exercise wheels (30.3 x 20.6 x 26 cm; Mini Mitter®, Nalgene® Activity Wheel for Rodents) at ten weeks of age, for three days (n=96). Six mice had their wheels locked to act as sedentary controls (sed). Animals were considered to be high runners (HR) if they ran >= 5 km/night and low runners (LR) if they ran <= 2 km/night. Middle runners (MR) were chosen randomly from the population of animals falling between the high and low groups. This series is comprised of array results from three parallel experiments comparing HR versus sed, MR versus sed, and HR versus LR. Six hybridizations were performed for each of the three comparisons (3 forward-labeled, 3-reverse labeled) to account for dye-incorporation differences. One slide from the HR vs LR experiment was broken during processing, so only five are included from that group. Keywords = hippocampus Keywords = voluntary running Keywords = voluntary exercise Keywords = C57Bl/6J Keywords: parallel sample
Project description:Effects of voluntary exercise in rat aorta. Spontaneously hypertensive rats (SHR) performed 5 weeks of voluntary exercise (wheel-cage running). Aortic tissue was collected and samples were pooled (3 aortae/chip). Aortae from running rats were compared to aortae from non-running rats. Keywords: parallel sample
Project description:Effects of voluntary exercise in rat aorta. Spontaneously hypertensive rats (SHR) performed 5 weeks of voluntary exercise (wheel-cage running). Aortic tissue was collected and samples were pooled (3 aortae/chip). Aortae from running rats were compared to aortae from non-running rats.
Project description:To undertake transcriptome-wide microarray analysis to develop a view of molecular adaptations that may underpin any benefit associated with the mild exercise regime of voluntary running Total RNA obtained from isolated whole hearts subjected to 7 days of voluntary exercise compared to sedentary control hearts (n=6/group).
Project description:Comparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy We performed microarray analysis on RNA from left ventricles of mice in non-pregnant diestrus cycle, mid-pregnancy (MP), late-pregnancy (LP), and immediate post-partum (0PP). These were compared to 7days (7EX) and 21 days (21EX) of voluntary wheel running exercise.
Project description:To undertake transcriptome-wide microarray analysis to develop a view of molecular adaptations that may underpin any benefit associated with the mild exercise regime of voluntary running
Project description:Voluntary running exercise after focal cerebral ischemia promotes functional recovery and prevents the ischemia-induced dendritic spine loss in the peri-infarct motor cortex layer 5. Neuronal morphology is affected by the perineuronal environmental change. Glia exert crucial roles in the formation of perineuronal environment, and exercise-induced changes of glial phenotype are expected. Here, we demonstrated that voluntary running exercise increased the population of newborn astrocytes in the acute phase after cerebral ischemia at late phase. Transcriptome analysis detected 10 upregulated genes and 70 downregulated genes by exercise in the ipsilateral cortex astrocytes. Gene cluster downregulated by exercise were significantly associated with neuronal morphology. The expression of Lipocalin 2, a factor of decreasing dendritic spines, tended to be decreased in the postischemic astrocytes by exercise. Our results suggest that exercise modifies the phenotype of postischemic astrocytes, which relate to the exercise-induced amelioration of postischemic dendritic spine loss.
Project description:Voluntary exercise reduces the risk of cancer and lowers the risk of disease recurrence. Yet the mechanisms for this protection remain to be elucidated. Here we demonstrate that exercise halves tumor growth through an exercise-dependent mobilization and intratumoral infiltration of NK cells in malignant melanoma. Using voluntary wheel running, we show that exercise prior to and during B16 tumor challenge reduced tumor growth by 67%, and this reduction was associated with increased inflammation and immune cell infiltrates, especially NK cells, in the tumors from exercising mice. Depletion of NK cells blunted the exercise-dependent reduction in tumor growth. Moreover, during exercise, NK cells were engaged through an epinephrine-dependent mobilization to the circulation and redistributed to peripheral tissues through an IL-6 dependent mechanism. This study highlights the importance of exercise-dependent immune regulation in the control of malignant melanoma Gene expression profile of melanoma tumor tissue from two groups of exercise and non-exercise mice
Project description:Gene expression and phenotypic consequences of laboratory housing in rats. Disease related-phenotypes and associated gene expressions of sedentary animals (living solely in a standard cage) were compared with animals that had access to twice-weekly one-hour physical activity in a large box (PA) and with those that had access to voluntary running wheel exercise (EX). Keywords: exercise dose reponse, sedentary, twice weekly physical activity, daily exercise