Dataset Information

Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways.

ABSTRACT: Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients is common. Neuromuscular Electrical Stimulation (NMES) is a powerful exercise training that may relieve muscle dysfunction in COPD. This study investigated whether electrical stimulation may have atypical adaptations via activation of miRNA related pathways in counteracting COPD muscle dysfunction. Forty-eight male Sprague-Dawley rats were randomly assigned to 3 groups. With the exception of the rats in the control group, the experimental rats were exposed to chronic intermittent hypoxia-hypercapnia (CIHH) (9?11%O2,5.5?6.5%CO2) for 2 or 4 weeks. Electrical stimulation was performed immediately after each CIHH session. Following assessment of the running capacity, biopsy samples were obtained from the gastrocnemius of the rats. The miR-1, miR-133a and miR-133b levels were measured, as well as their related proteins: phosphorylation of Akt (p-AKT), PGC-1alpha (PGC-1?), histone deacetylase 4 (HDAC4) and serum response factor (SRF). Myosin heavy chainIIa (MHCIIa) and myosin heavy chainIIb (MHCIIb) were also measured to assess fiber type changes. After 2 weeks, compared with the controls, only miR-1 and miR-133a were significantly increased (p<0.05) in the exposure group. After 4 weeks, the exposure group exhibited a decreased running distance (p = 0.054) and MHCIIa-to-MHCIIb shift (p<0.05). PGC-1? (p = 0.051), nuclear HDAC4 (p = 0.058), HDAC4, p-AKT, PGC-1? and SRF was also significantly decreased (p<0.05). In contrast, miR-1 and miR-133a were significantly increased (p<0.05). Four weeks of electrical stimulation can partly reversed those changes, and miR-133b exhibited a transient increase after 2 weeks electrical stimulation. Our study indicate miRNAs may have roles in the response of CIHH-impaired muscle to changes during electrical stimulation.

SUBMITTER: Pan LL

PROVIDER: S-EPMC4811440 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways.

Pan Lu-Lu LL Ke Jiang-Qiong JQ Zhao Cui-Cui CC Huang Shi-Yuan SY Shen Jie J Jiang Xian-Xun XX Wang Xiao-Tong XT

PloS one 20160329 3

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients is common. Neuromuscular Electrical Stimulation (NMES) is a powerful exercise training that may relieve muscle dysfunction in COPD. This study investigated whether electrical stimulation may have atypical adaptations via activation of miRNA related pathways in counteracting COPD muscle dysfunction. Forty-eight male Sprague-Dawley rats were randomly assigned to 3 groups. With the exception of the rats in the cont ...[more]

PMID: 27023369

Similar Datasets

Project description:ObjectiveTo determine if Functional Electrical Stimulation (FES) would improve ischemic pain, walking distance, and quality of life of patients with intermittent claudication.DesignSingle blind, randomized block, two factorial design.PatientsPatients diagnosed with Peripheral Artery Disease (PAD) and intermittent claudication (IC). Ankle Brachial Index ranged 0.4-0.9 on at least one leg. Patients were randomly assigned to experimental (FES+Walk, N=13) or control (WALK, N=14) groups.InterventionExperimental group patients received FES to the dorsiflexor and plantarflexor muscles while walking for 1h/day, six days/week for eight weeks. Control group patients received similar intervention without FES. A Follow-up period of both groups lasted eight weeks.Outcome measuresOutcome measures were taken at baseline (T0), after intervention (T1), and after follow-up (T2). Primary measures included Perceived Pain Intensity (PPI), Six minute walk (6MW), and Peripheral Arterial Disease Quality of Life (PADQOL). Secondary measures included Intermittent Claudication Questionnaire (ICQ) and Timed Up and Go (TUG).ResultsGroup by time interactions in PPI were significant (P<0.001) with differences of 27.9 points at T1 and 36.9 points at T2 favoring the FES+Walk group. Groups difference in Symptoms and Limitations in Physical Function of the PADQOL reached significance (T1=8.9, and T2=8.3 improvements; P=0.007). ICQ was significant (T1=9.3 and T2=13.1 improvements; P=0.003). Improvement in 6MW and TUG tests were similar between groups.Conclusions and relevanceWalking with FES markedly reduced ischemic pain and enhanced QOL compared to just walking. FES while walking may offer an effective treatment option for the elderly with PAD and Intermittent Claudication.Trial registrationNIH-NIA 1R21AG048001 https://projectreporter.nih.gov/project_info_description.cfm?aid=8748641&icde=30695377&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC. https://clinicaltrials.gov/ct2/show/NCT02384980?term=David+Embrey&rank=1.

Project description:Obstructive sleep apnea (OSA), characterized by intermittent hypoxia and hypercapnia (IHC), affects the composition of the gut microbiome and metabolome. The gut microbiome has diurnal oscillations that play a crucial role in regulating circadian and overall metabolic homeostasis. Thus, we hypothesized that IHC adversely alters the gut luminal dynamics of key microbial families and metabolites. The objective of this study was to determine the diurnal dynamics of the fecal microbiome and metabolome of Apoe-/- mice after a week of IHC exposure. Individually housed, 10-week-old Apoe-/- mice on an atherogenic diet were split into two groups. One group was exposed to daily IHC conditions for 10 h (Zeitgeber time 2 [ZT2] to ZT12), while the other was maintained in room air. Six days after the initiation of the IHC conditions, fecal samples were collected every 4 h for 24 h (6 time points). We performed 16S rRNA gene amplicon sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) to assess changes in the microbiome and metabolome. IHC induced global changes in the cyclical dynamics of the gut microbiome and metabolome. Ruminococcaceae, Lachnospiraceae, S24-7, and Verrucomicrobiaceae had the greatest shifts in their diurnal oscillations. In the metabolome, bile acids, glycerolipids (phosphocholines and phosphoethanolamines), and acylcarnitines were greatly affected. Multi-omic analysis of these results demonstrated that Ruminococcaceae and tauro-β-muricholic acid (TβMCA) cooccur and are associated with IHC conditions and that Coriobacteriaceae and chenodeoxycholic acid (CDCA) cooccur and are associated with control conditions. IHC significantly change the diurnal dynamics of the fecal microbiome and metabolome, increasing members and metabolites that are proinflammatory and proatherogenic while decreasing protective ones. IMPORTANCE People with obstructive sleep apnea are at a higher risk of high blood pressure, type 2 diabetes, cardiac arrhythmias, stroke, and sudden cardiac death. We wanted to understand whether the gut microbiome changes induced by obstructive sleep apnea could potentially explain some of these medical problems. By collecting stool from a mouse model of this disease at multiple time points during the day, we studied how obstructive sleep apnea changed the day-night patterns of microbes and metabolites of the gut. Since the oscillations of the gut microbiome play a crucial role in regulating metabolism, changes in these oscillations can explain why these patients can develop so many metabolic problems. We found changes in microbial families and metabolites that regulate many metabolic pathways contributing to the increased risk for heart disease seen in patients with obstructive sleep apnea.

Project description:Studying perturbations in the gut ecosystem using animal models of disease continues to provide valuable insights into the role of the microbiome in various pathological conditions. However, understanding whether these changes are consistent across animal models of different genetic backgrounds, and hence potentially translatable to human populations, remains a major unmet challenge in the field. Nonetheless, in relatively limited cases have the same interventions been studied in two animal models in the same laboratory. Moreover, such studies typically examine a single data layer and time point. Here, we show the power of utilizing time series microbiome (16S rRNA amplicon profiling) and metabolome (untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) data to relate two different mouse models of atherosclerosis-ApoE-/- (n = 24) and Ldlr-/- (n = 16)-that are exposed to intermittent hypoxia and hypercapnia (IHH) longitudinally (for 10 and 6 weeks, respectively) to model chronic obstructive sleep apnea. Using random forest classifiers trained on each data layer, we show excellent accuracy in predicting IHH exposure within ApoE-/- and Ldlr-/- knockout models and in cross-applying predictive features found in one animal model to the other. The key microbes and metabolites that reproducibly predicted IHH exposure included bacterial species from the families Mogibacteriaceae, Clostridiaceae, bile acids, and fatty acids, providing a refined set of biomarkers associated with IHH. The results highlight that time series multiomics data can be used to relate different animal models of disease using supervised machine learning techniques and can provide a pathway toward identifying robust microbiome and metabolome features that underpin translation from animal models to human disease. IMPORTANCE Reproducibility of microbiome research is a major topic of contemporary interest. Although it is often possible to distinguish individuals with specific diseases within a study, the differences are often inconsistent across cohorts, often due to systematic variation in analytical conditions. Here we study the same intervention in two different mouse models of cardiovascular disease (atherosclerosis) by profiling the microbiome and metabolome in stool specimens over time. We demonstrate that shared microbial and metabolic changes are involved in both models with the intervention. We then introduce a pipeline for finding similar results in other studies. This work will help find common features identified across different model systems that are most likely to apply in humans.

Project description:Obstructive sleep apnea (OSA) is a common disorder characterized by episodic obstruction to breathing due to upper airway collapse during sleep. Because of the episodic airway obstruction, intermittently low O2 (hypoxia) and high CO2 (hypercapnia) ensue. OSA has been associated with adverse cardiovascular and metabolic outcomes, although data regarding potential causal pathways are still evolving. As changes in inspired O2 and CO2 can affect the ecology of the gut microbiota and the microbiota has been shown to contribute to various cardiometabolic disorders, we hypothesized that OSA alters the gut ecosystem, which, in turn, exacerbates the downstream physiological consequences. Here, we model human OSA and its cardiovascular consequence using Ldlr-/- mice fed a high-fat diet and exposed to intermittent hypoxia and hypercapnia (IHH). The gut microbiome and metabolome were characterized longitudinally (using 16S rRNA amplicon sequencing and untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) and seen to covary during IHH. Joint analysis of microbiome and metabolome data revealed marked compositional changes in both microbial (>10%, most remarkably in Clostridia) and molecular (>22%) species in the gut. Moreover, molecules that altered in abundance included microbe-dependent bile acids, enterolignans, and fatty acids, highlighting the impact of IHH on host-commensal organism cometabolism in the gut. Thus, we present the first evidence that IHH perturbs the gut microbiome functionally, setting the stage for understanding its involvement in cardiometabolic disorders. IMPORTANCE Intestinal dysbiosis mediates various cardiovascular diseases comorbid with OSA. To understand the role of dysbiosis in cardiovascular and metabolic disease caused by OSA, we systematically study the effect of intermittent hypoxic/hypercapnic stress (IHH, mimicking OSA) on gut microbes in an animal model. We take advantage of a longitudinal study design and paired omics to investigate the microbial and molecular dynamics in the gut to ascertain the contribution of microbes on intestinal metabolism in IHH. We observe microbe-dependent changes in the gut metabolome that will guide future research on unrecognized mechanistic links between gut microbes and comorbidities of OSA. Additionally, we highlight novel and noninvasive biomarkers for OSA-linked cardiovascular and metabolic disorders.

Project description:Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg) for 180 min. The mean artery pressure (MAP), blood gas, and cerebral blood flow (CBF) were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4) expression. In rats treated with severe hypoxia (PaO2 < 50 mmHg), hypercapnia augmented the decline of MAP with cortical CBF and damaged blood-brain barrier permeability (p < 0.05). In contrast, in rats treated with mild to moderate hypoxia (PaO2 > 50 mmHg), hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg); especially under mild hypoxemia (PaO2 > 60 mmHg), hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05). Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

Dataset Information

Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways.

Publications

Electrical Stimulation Improves Rat Muscle Dysfunction Caused by Chronic Intermittent Hypoxia-Hypercapnia via Regulation of miRNA-Related Signaling Pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets