Influence of low and high force muscle activity on paralyzed muscle gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE64683 | GEO | 2015/08/01
SECONDARY ACCESSION(S): PRJNA271619
REPOSITORIES: GEO
Similar Datasets
Project description:We used a novel approach to study the acute effect of two frequencies of stimulation (20 Hz and 5 Hz; high and low force, respectively) on gene regulation in people with chronic paralysis. Three hours after the completion of the electrical stimulation protocol (5 Hz or 20 Hz), we sampled the vastus lateralis muscle and examined genes involved with metabolic transcription, glycolysis, oxidative phosphorylation, and mitochondria remodelling. We discovered that the 5 Hz stimulation, despite generating a lower overall force, induced a 5-6 fold increase (p<0.05) in key metabolic transcription factors including PGC-1?, NR4A3, and ABRA. Neither protocol showed a robust regulation of genes for glycolysis, oxidative phosphorylation, and mitochondria remodelling. We analyzed skeletal muscle using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Partek Genomic Suites.
2015-08-01 | E-GEOD-64683 | biostudies-arrayexpress
Project description:Adult male Swiss Webster mice (30-35 g) were anesthetized, a bipolar electrode was implanted adjacent to the sciatic nerve and the hindlimb immobilized. The voltage-force relation was determined to establish supramaximal stimulation conditions and the length-tension relation was determined to set the resting length for maximum twitch tension. Contractions were induced by sciatic nerve stimulation (0.5 msec duration, 2-5 volts). The muscles were allowed to rest 15 minutes for full metabolic recovery at physiologic temperatures. Supramaximal stimulation was applied at a rate of 10 Hz for 4 hours. At the end of each experiment the extensor digitorum longus (EDL) muscles were carefully dissected and flash frozen in liquid nitrogen for analysis of mRNA expression via microarray analysis. The contralateral, unstimulated EDL provided a genetically matched, paired control for each specimen.
2010-06-01 | GSE10454 | GEO
Project description:Stimulation of the mouse hindlimb via the sciatic nerve was used to induce contractions for 4 hours to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 + 0.1 g/g body weight) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon completion of the study. An immediate-early growth response was present in the EDL (FOS, JUN, ATF3, MAFK) with a similar but attenuated pattern in the soleus. Transcript profiles showed decreased fast fiber specific mRNA (myosin heavy chains 2A, 2B; troponins T3, I; -tropomyosin, m-creatine kinase) and increased slow transcripts (myosin heavy chain slow/1, troponin C, tropomyosin 3) in the EDL. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration or myofiber damage in stimulated vs. control muscles. Several fiber type specific transcription factors (EYA1, TEAD1, NFATc1 and c4, PPARG, PPARGC1 and β, BHLHB2) increased in the EDL along with transcription factors characteristic of embryogenesis (KLF4, SOX17, TCF15, PKNOX1, ELAV). No established in vivo satellite cell markers or the genes activated during our parallel studies of satellite cell proliferation in vitro (CYCLINS A2, B2, C, E1, MyoD) increased in the stimulated muscles. These data indicated that onset of fast to slow phenotype conversion occurred in the EDL within 4 hours of stimulation without satellite cell recruitment or muscle injury but was driven by phenotype specific transcription factors from resident fiber myonuclei including activation of nascent developmental transcriptional programs. Adult male Swiss Webster mice (30-35 g) were anesthetized, a bipolar electrode was implanted adjacent to the sciatic nerve and the hindlimb immobilized. The voltage-force relation was determined to establish supramaximal stimulation conditions and the length-tension relation was determined to set the resting length for maximum twitch tension. Contractions were induced by sciatic nerve stimulation (0.5 msec duration, 2-5 volts). The muscles were allowed to rest 15 minutes for full metabolic recovery at physiologic temperatures. Supramaximal stimulation was applied at a rate of 10 Hz for 4 hours. At the end of each experiment the soleus muscles were carefully dissected and flash frozen in liquid nitrogen for analysis of mRNA expression via microarray analysis. The contralateral, unstimulated Soleus provided a genetically matched, paired control for each specimen.
2010-06-01 | E-GEOD-14391 | biostudies-arrayexpress
Project description:Aims: Transforming growth factor-β (TGF-β) signalling is thought to contribute to the remodelling of extracellular matrix (ECM) of skeletal muscle and to functional decline in patients with muscular dystrophies. We wanted to determine the role of TGF-β-induced ECM remodelling in dystrophic muscle. Methods: We experimentally induced the pathological hallmarks of severe muscular dystrophy by mechanically overloading the plantaris muscle in mice. Furthermore, we determined the role of TGF-β signalling on dystrophic tissue modulation and on muscle function by (i) overloading myostatin knockout (Mstn-/- ) mice and (ii) by additional pharmacological TGF-β inhibition via halofuginone. Results: Transcriptome analysis of overloaded muscles revealed upregulation predominantly of genes associated with ECM, inflammation and metalloproteinase activity. Histology revealed in wild-type mice signs of severe muscular dystrophy including myofibres with large variation in size and internalized myonuclei, as well as increased ECM deposition. At the same time, muscle weight had increased by 208% and muscle force by 234%. Myostatin deficiency blunted the effect of overload on muscle mass (59% increase) and force (76% increase), while having no effect on ECM deposition. Concomitant treatment with halofuginone blunted overload-induced muscle hypertrophy and muscle force increase, while reducing ECM deposition and increasing myofibre size. Conclusions: ECM remodelling is associated with an increase in muscle mass and force in overload-modelled dystrophic muscle. Lack of myostatin is not advantageous and inhibition of ECM deposition by halofuginone is disadvantageous for muscle plasticity in response to stimuli that induce dystrophic muscle.
2020-08-01 | GSE127255 | GEO
Project description:To begin to validate potential causal regulators of muscle function, we targeted genes containing novel skeletal muscle pQTLs and molecular/phenotypic associations, and performed a functional genomic screen in human skeletal muscle organoids (PMID: 30527761). We focused on proteins with negative associations to lean mass, grip strength or other metabolic associations, and generated a total of 27 individual rAAV6:shRNAs. Organoids were grown around contraction posts to monitor contractile force production during electrical stimulation, and transduced following differentiation and maturation to limit effects on the myogenic program (Figure 3A). Electrical stimulation was performed to induce either a tetanic contraction for assessment of maximum force production or stimulated with sustained lower frequency for assessment of fatigue. Following the protocol, organoids were analysed by proteomics which quantified 17/27 targets with 13 targets significantly reduced in abundance by rAAV6:shRNA.
2023-01-08 | PXD034913 | Pride
Project description:Extracellular matrix remodelling is associated with muscle force increase in overloaded mouse plantaris muscle.
| PRJNA524535 | ENA
Project description:Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to simultaneously contract multiple muscle groups. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly via mitochondrial biosynthesis. In this study, we examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for 1 week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague Dawley rats using belt electrodes attached to both ankle joints. In acute stimulation, a significant decrease in glycogen content in the left and right TA and GAS was observed, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES also enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN+electrically stimulated with B-SES (DEN＋ES) groups. After 7 days of treatment, muscle wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN+ES groups compared to those in the CON group. The DEN+ES group showed significantly higher muscle weight and CSA than the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial and ribosome biogenesis are key events in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 45S (n = 6) levels in the DEN+ES group were higher than those in the DEN group. The mRNA levels of the muscle proteolytic molecules Atrogin-1 and MuRF1 were significantly higher in DEN than in CONT but were suppressed in DEN+ES. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes was effective in preventing denervation-induced atrophy in multiple muscle groups. Unlike twitch contractions, ribosomal biosynthesis plays a key role in tetanic contractions to prevent muscle atrophy.
2024-01-06 | E-MTAB-13286 | biostudies-arrayexpress
Project description:Analysis of the effect of electrical field stimulation frequency at the gene expression level. Electrical stimulation has been shown to mature nascent cardiomyocytes and alter their beating properties. The purpose of the array was to identify potential mediators of these effects. Total RNA was isolated from cardiomyocytes subjected to 0.5 Hz, 1 Hz, or 2 Hz continuous electrical stimulation for 7 days, compared to an unstimulated control. Three samples from each group were analyzed
2015-11-05 | E-GEOD-74669 | biostudies-arrayexpress
Project description:We investigated the short and long term effects of electrically induced exercise on mRNA expression of human paralyzed muscle. We developed an exercise dose that activated the muscle for 0.6% of the day. The short term effects were assessed 3 hours after a single dose of exercise, while the long term effects were assessed after training 5 days per week for at least one year (adherence 81%). A single dose of electrical stimulation increased the mRNA expression of transcriptional, translational, and enzyme regulators of metabolism important to shift muscle toward an oxidative phenotype (PGC-1a, NR4A3, IFRD1, ABRA, PDK4). However, chronic training increased the mRNA expression of specific metabolic pathway genes (BRP44, BRP44L, SDHB, ACADVL), mitochondrial fission and fusion genes (MFF, MFN1, MFN2), and slow muscle fiber genes (MYH6, MYH7, MYL3, MYL2).Furthermore, regulating these same pathways may be critical to developing efficient activity protocols to reduce the prevalence of diabetes in people with longstanding paralysis from SCI. We analyzed skeletal muscle using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Partek Genomic Suites.
2015-09-01 | E-GEOD-63423 | biostudies-arrayexpress
Project description:We investigated the short and long term effects of electrically induced exercise on mRNA expression of human paralyzed muscle. We developed an exercise dose that activated the muscle for 0.6% of the day. The short term effects were assessed 3 hours after a single dose of exercise, while the long term effects were assessed after training 5 days per week for at least one year (adherence 81%). A single dose of electrical stimulation increased the mRNA expression of transcriptional, translational, and enzyme regulators of metabolism important to shift muscle toward an oxidative phenotype (PGC-1a, NR4A3, IFRD1, ABRA, PDK4). However, chronic training increased the mRNA expression of specific metabolic pathway genes (BRP44, BRP44L, SDHB, ACADVL), mitochondrial fission and fusion genes (MFF, MFN1, MFN2), and slow muscle fiber genes (MYH6, MYH7, MYL3, MYL2).Furthermore, regulating these same pathways may be critical to developing efficient activity protocols to reduce the prevalence of diabetes in people with longstanding paralysis from SCI.
2015-09-01 | GSE63423 | GEO