scholarly journals Low-frequency Electrical Stimulation Alleviates Immobilization-evoked Disuse Muscle Atrophy via Repressing Autophagy in Skeletal Muscle of Rabbits

2021 ◽  
Author(s):  
A-Ying Liu ◽  
Quan-Bing Zhang ◽  
Hua-Long Zhu ◽  
Yong-Wei Xiong ◽  
Feng Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Knee Joint ◽  
Muscle Atrophy ◽  
Rabbit Model ◽  
Low Frequency ◽  
Cross Sectional ◽  
Disuse Muscle Atrophy ◽  
Joint Range ◽  
Time Point

Abstract Objective: The present study was to investigate the effect of low-frequency electrical stimulation on disuse muscle atrophy and its mechanism in a rabbit model of extending knee joint contracture.Methods: This study designed two experiments. In the time-point experiment, 24 rabbits were randomly divided into Control 1(Ctrl1), immobilization for 2 weeks (I-2), I-4, and I-6 groups. In the intervention experiment, 24 rabbits were also randomly divided into Control 2 (Ctrl2), electrical stimulation (ES), natural recovery (NR) and electrical stimulation treatment (EST) groups. All intervention effects were assessed by evaluating the knee joint range of motion (ROM), cross-sectional area (CSA) of muscle and the expression of autophagy-related proteins.Results: Time-point experiment showed that immobilization reduced knee ROM, muscle CSA, and activated autophagy in skeletal muscle. Levels of four autophagic proteins including p-mTOR, Atg7, p62 and LC3B-II, were significantly elevated in the skeletal muscle of I-4 group. The intervention experiment further presented that LFES significantly improved the immobilization-induced ROM and CSA reduction. Additionally, LFES significantly reversed autophagy activation of skeletal muscle caused by immobilization.Conclusions: Low-frequency electrical stimulation alleviates immobilization-evoked disuse muscle atrophy maybe via inhibiting autophagy in skeletal muscle of rabbits.

scholarly journals Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Atrophy ◽  
Microgravity Environment ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

scholarly journals Changes in Gene Expression of the MCU Complex Are Induced by Electrical Stimulation in Adult Skeletal Muscle

2021 ◽  
Vol 11 ◽  
Author(s):  
Esteban R. Quezada ◽  
Alexis Díaz-Vegas ◽  
Enrique Jaimovich ◽  
Mariana Casas
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscle Fibers ◽  
Low Frequency ◽  
Extracellular Atp ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adult Skeletal Muscle ◽  
Muscle Plasticity

The slow calcium transient triggered by low-frequency electrical stimulation (ES) in adult muscle fibers and regulated by the extracellular ATP/IP3/IP3R pathway has been related to muscle plasticity. A regulation of muscular tropism associated with the MCU has also been described. However, the role of transient cytosolic calcium signals and signaling pathways related to muscle plasticity over the regulation of gene expression of the MCU complex (MCU, MICU1, MICU2, and EMRE) in adult skeletal muscle is completely unknown. In the present work, we show that 270 0.3-ms-long pulses at 20-Hz ES (and not at 90 Hz) transiently decreased the mRNA levels of the MCU complex in mice flexor digitorum brevis isolated muscle fibers. Importantly, when ATP released after 20-Hz ES is hydrolyzed by the enzyme apyrase, the repressor effect of 20 Hz on mRNA levels of the MCU complex is lost. Accordingly, the exposure of muscle fibers to 30 μM exogenous ATP produces the same effect as 20-Hz ES. Moreover, the use of apyrase in resting conditions (without ES) increased mRNA levels of MCU, pointing out the importance of extracellular ATP concentration over MCU mRNA levels. The use of xestospongin B (inhibitor of IP3 receptors) also prevented the decrease of mRNA levels of MCU, MICU1, MICU2, and EMRE mediated by a low-frequency ES. Our results show that the MCU complex can be regulated by electrical stimuli in a frequency-dependent manner. The changes observed in mRNA levels may be related to changes in the mitochondria, associated with the phenotypic transition from a fast- to a slow-type muscle, according to the described effect of this stimulation frequency on muscle phenotype. The decrease in mRNA levels of the MCU complex by exogenous ATP and the increase in MCU levels when basal ATP is reduced with the enzyme apyrase indicate that extracellular ATP may be a regulator of the MCU complex. Moreover, our results suggest that this regulation is part of the axes linking low-frequency stimulation with ATP/IP3/IP3R.

scholarly journals Effects of combined treatment with blood flow restriction and low-current electrical stimulation on muscle hypertrophy in rats

2019 ◽  
Vol 127 (5) ◽  
pp. 1288-1296
Author(s):  
Madoka Yoshikawa ◽  
Takeshi Morifuji ◽  
Tomohiro Matsumoto ◽  
Noriaki Maeshige ◽  
Minoru Tanaka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Electrical Stimulation ◽  
Muscle Hypertrophy ◽  
Combined Treatment ◽  
Blood Flow Restriction ◽  
Sectional Area ◽  
Cross Sectional ◽  
Flow Restriction ◽  
Skeletal Muscle Hypertrophy

This study aimed to clarify the effects of a combined treatment comprising blood flow restriction and low-current electrical stimulation on skeletal muscle hypertrophy in rats. Male Wistar rats were divided into control (Cont), blood flow restriction (Bfr), electrical stimulation (Es), or Bfr with Es (Bfr + Es) groups. Pressure cuffs (80 mmHg) were placed around the thighs of Bfr and Bfr + Es rats. Low-current Es was applied to calf muscles in the Es and Bfr + Es rats. In experiment 1, a 1-day treatment regimen (5-min stimulation, followed by 5-min rest) was delivered four times to study the acute effects. In experiment 2, the same treatment regimen was delivered three times/wk for 8 wk. Body weight, muscle mass, changes in maximal isometric contraction, fiber cross-sectional area of the soleus muscle, expression of phosphorylated and total-ERK1/2, phosphorylated-rpS6 Ser235/236, phosphorylated and total Akt, and phosphorylated-rpS6 Ser240/244 were measured. Bfr and Es treatment alone failed to induce muscle hypertrophy and increase the expression of phosphorylated rpS6 Ser240/244. Combined Bfr + Es upregulated muscle mass, increased the fiber cross-sectional area, and increased phosphorylated rpS6 Ser240/244 expression and phosphorylated rpS6 Ser235/236 expression compared with controls. Combined treatment with Bfr and low-current Es can induce muscle hypertrophy via activation of two protein synthesis signaling pathways. This treatment should be introduced for older patients with sarcopenia and others with muscle weakness. NEW & NOTEWORTHY We investigated the acute and chronic effect of low-current electrical stimulation with blood flow restriction on skeletal muscle hypertrophy and the mechanisms controlling the hypertrophic response. Low-current electrical stimulation could not induce skeletal muscle hypertrophy, but a combination treatment did. Blood lactate and growth hormone levels were increased in the early response. Moreover, activation of ERK1/2 and mTOR pathways were observed in both the acute and chronic response, which contribute to muscle hypertrophy.

scholarly journals β-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2180
Author(s):  
Mari Noguchi ◽  
Tomoya Kitakaze ◽  
Yasuyuki Kobayashi ◽  
Katsuyuki Mukai ◽  
Naoki Harada ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Muscle Fibers ◽  
Skeletal Muscle Atrophy ◽  
Related Factor ◽  
Related Factors ◽  
Cross Sectional ◽  
Senescence Accelerated Mouse

We investigated the effects of β-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or β-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. β-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, β-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, β-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. β-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, β-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the β-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that β-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

scholarly journals Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization

2018 ◽  
Vol 33 (01) ◽  
pp. 015-021 ◽  
Author(s):  
Yun Zhou ◽  
Quan Bing Zhang ◽  
Hua Zhang Zhong ◽  
Yi Liu ◽  
Jun Li ◽  
...  
Keyword(s):  
Knee Joint ◽  
Range Of Motion ◽  
Rabbit Model ◽  
Joint Capsule ◽  
Joint Contracture ◽  
Control Group ◽  
Mrna Levels ◽  
Joint Range Of Motion ◽  
Joint Range ◽  
Tgf Β1

AbstractThis study aimed to develop a rabbit model of knee contracture in extension and investigate the natural history of motion loss and time-dependent changes in the joint capsule after immobilization. We immobilized the unilateral knee joints of 32 rabbits by maintaining the knee joint in a plaster cast at full extension. Eight rabbits were euthanized at 2, 4, 6, and 8 weeks after casting, respectively, and the lower extremities were disarticulated at the hip joint. Eight control group rabbits that did not undergo immobilization were also examined. We assessed the progression of joint contracture by measuring the joint range of motion, evaluating the histologic alteration of the capsule, and assessing the mRNA levels of transforming growth factor β1 (TGF-β1) in the anterior and posterior joint capsules. After 2 weeks of joint immobilization, the knee joint range of motion was limited, the synovial membrane of the suprapatellar and posterior joint capsules was thickened, the collagen deposition was increased, and the mRNA levels of TGF-β1 were elevated in the anterior and posterior joint capsules. These changes progressed rapidly until 6 weeks of immobilization and may advance slowly after 6 weeks. Joint contracture developed at the early stage of immobilization and progressed over time. The changes in the anterior and posterior joint capsules after joint immobilization may contribute to the limitation in flexion. The elevated mRNA expression of TGF-β1 may be related to joint capsule fibrosis and may be one of the causes of joint contracture.

Excitation-induced Ca2+uptake in rat skeletal muscle

1999 ◽  
Vol 276 (2) ◽  
pp. R331-R339 ◽  
Author(s):  
H. Gissel ◽  
T. Clausen
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Initial Rate ◽  
Low Frequency ◽  
Channel Blockers ◽  
Ca Uptake ◽  
Edl Muscle ◽  
Isotonic Contractions ◽  
Progressive Accumulation ◽  
Stimulation Of

In isolated rat extensor digitorum longus (EDL) muscle mounted for isometric contractions, chronic low-frequency electrical stimulation was found to lead to an increased uptake of45Ca (154% above control after 240 min) and a progressive accumulation of Ca2+ (85% above control after 240 min). In soleus, however, this treatment led to a small, but significant, increase in 45Ca uptake (30% above control after 180 min) but no significant accumulation of Ca2+. In muscles mounted for isotonic contractions without any external load, electrical stimulation gave rise to a larger45Ca uptake and accumulation of Ca2+ in both EDL and soleus. These uptakes of Ca2+ coincided with an accumulation of Na+. During isometric or isotonic contractions, stimulation at 40 Hz increased the initial (60 s) rate of 45Ca uptake in soleus muscle 15- and 30-fold, respectively. The stimulation-induced increase in 45Ca uptake was only reduced by 17% by the Ca2+-channel blockers nifedipine and verapamil but was blocked by tetrodotoxin. The initial rate of stimulation-induced 22Na and45Ca uptake was correlated ( r = 0.80; P < 0.003). Stimulation of Na+ channels with veratridine increased 45Ca uptake by 93 and 139% in soleus and EDL, respectively ( P < 0.001), effects that were abolished by tetrodotoxin. The results indicate that in skeletal muscle, excitation induces a considerable influx of Ca2+, mediated by Na+ channels.

scholarly journals FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70

2010 ◽  
Vol 298 (1) ◽  
pp. C38-C45 ◽  
Author(s):  
Sarah M. Senf ◽  
Stephen L. Dodd ◽  
Andrew R. Judge
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Fiber ◽  
Muscle Wasting ◽  
Dominant Negative ◽  
Disuse Muscle Atrophy ◽  
Rat Soleus Muscle ◽  
Muscle Fiber Atrophy ◽  
Fiber Atrophy

The purpose of the current study was to determine whether heat shock protein 70 (Hsp70) directly regulates forkhead box O (FOXO) signaling in skeletal muscle. This aim stems from previous work demonstrating that Hsp70 overexpression inhibits disuse-induced FOXO transactivation and prevents muscle fiber atrophy. However, although FOXO is sufficient to cause muscle wasting, no data currently exist on the requirement of FOXO signaling in the progression of physiological muscle wasting, in vivo. In the current study we show that specific inhibition of FOXO, via expression of a dominant-negative FOXO3a, in rat soleus muscle during disuse prevented >40% of muscle fiber atrophy, demonstrating that FOXO signaling is required for disuse muscle atrophy. Subsequent experiments determined whether Hsp70 directly regulates FOXO3a signaling when independently activated in skeletal muscle, via transfection of FOXO3a. We show that Hsp70 inhibits FOXO3a-dependent transcription in a gene-specific manner. Specifically, Hsp70 inhibited FOXO3a-induced promoter activation of atrogin-1, but not MuRF1. Further studies showed that a FOXO3a DNA-binding mutant can activate MuRF1, but not atrogin-1, suggesting that FOXO3a activates these two genes through differential mechanisms. In summary, FOXO signaling is required for physiological muscle atrophy and is directly inhibited by Hsp70.

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