Low-frequency electrical stimulation alleviates immobilization-evoked disuse muscle atrophy by repressing autophagy in skeletal muscle of rabbits.

BACKGROUND: The study aimed to investigate the effect of low-frequency electrical stimulation (LFES) on disuse muscle atrophy and its mechanism in a rabbit model of knee extension contracture. METHODS: This study involved two experiments. In the time-point experiment, 24 rabbits were randomly divided into 4 groups: Control 1 (Ctrl1 group), immobilization for 2 weeks (I-2 group), immobilization for 4 weeks (I-4 group), and immobilization for 6 weeks (I-6 group). In the intervention experiment, 24 rabbits were randomly divided into 4 groups: Control 2 (Ctrl2 group), electrical stimulation (ESG group), natural recovery (NRG group), and electrical stimulation treatment (ESTG group). All intervention effects were assessed by evaluating the knee joint range of motion (ROM), cross-sectional area (CSA) of the rectus femoris muscle, and expression of autophagy-related proteins. RESULTS: The time-point experiment showed that immobilization reduced the knee ROM, reduced the rectus femoris muscle CSA, and activated autophagy in skeletal muscle. The levels of five autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), autophagy-related protein 7 (Atg7), p62, and microtubule-associated protein light chain 3B-II (LC3B-II)] were significantly elevated in the skeletal muscle of the I-4 group. The intervention experiment further showed that LFES significantly improved the immobilization-induced reductions in ROM and CSA. Additionally, LFES resulted in a significant decrease in the protein expression of mTOR, p-mTOR, Atg7, p62, and LC3B-II in the rectus femoris muscle. CONCLUSIONS: LFES alleviates immobilization-evoked disuse muscle atrophy possibly by inhibiting autophagy in the skeletal muscle of rabbits.

Effect of Electrical Stimulation on Disuse Muscular Atrophy Induced by Immobilization: Correlation With Upregulation of PERK Signal and Parkin-Mediated Mitophagy.

OBJECTIVES: The aims of the study are to investigate the effect of electrical stimulation on disuse muscular atrophy induced by immobilization (IM) and to explore the role of PERK signal and Parkin-dependent mitophagy in this process. DESIGN: In the first subexperiment, 24 rabbits were divided into four groups, which underwent different periods of IM. In the second subexperiment, 24 rabbits were divided into four groups on average in accordance with different kinds of interventions. To test the time-dependent changes of rectus femoris after IM, and to evaluate the effect of electrical stimulation, the wet weights, cross-sectional area and fat deposition of rectus femoris were assessed in this study, along with the protein levels of atrogin-1, p-PERK, Parkin, and COXIV. RESULTS: The wet weights and cross-sectional area decreased, and the fat deposition increased in rectus femoris after IM, along with the elevated protein levels of atrogin-1, p-PERK, Parkin, and decreased protein levels of COXIV. The above histomorphological and molecular changes can be partially ameliorated by electrical stimulation. CONCLUSIONS: Immobilization of unilateral lower limb could induce rectus femoris atrophy, which can be partially rectified by electrical stimulation. PERK signal and Parkin-mediated mitophagy may be the mechanisms by which electrical stimulation can play a significant role.

[Role of autophagy in the maintenance of skeletal muscle mass].

As an important exercise and energy metabolism organ of the human body, the normal maintenance of skeletal muscle mass is essential for the body to perform normal physiological functions. The autophagy-lysosome (AL) pathway is a physiological or pathological mechanism that is ubiquitous in normal and diseased cells. It plays a key role in the maintaining of protein balance, removing damaged organelles, and the stability of internal environment. The smooth progress of the autophagy process needs to go through multiple steps, which are completed under the coordinated action of multiple factors. Autophagy maintains the muscle homeostasis of a healthy body by removing cell components such as damaged myofibrils and isolated cytoplasmic proteins. Autophagy could also provide the initial energy required for cell proliferation, promote muscle regeneration and remodeling after injury. At the same time, autophagy disorder is also an important cause of age-related skeletal muscle atrophy. Autophagy could affect the response of skeletal muscle to exercise, and increasing the level of basic autophagy is beneficial to improve the adaptive response of skeletal muscle to exercise. This article summarizes the role and pathways of autophagy in the maintenance of skeletal muscle quality, in order to provide effective rehabilitation strategies for clinical prevention and treatment of muscle atrophy.

Preventive effect and possible mechanisms of ultrashort wave diathermy on myogenic contracture in a rabbit model.

The purpose of this study was to determine the preventive effect of ultrashort wave diathermy on immobilization-induced myogenic contracture and to explore its underlying mechanisms. Forty-two rabbits were randomly assigned into control (Group C), immobilization (Group I, which was further divided into one week, Group I-1; two weeks, Group I-2; and four weeks, Group I-4, subgroups by the length of immobilization) and ultrashort wave prevention (Group U, which was further divided into one week, Group U-1; two weeks, Group U-2; and four weeks, Group U-4, by time of treatment) groups. Intervention effects were assessed by evaluating rectus femoris cross-sectional area (CSA), knee range of motion, and the protein levels for myogenic differentiation (MyoD) and muscle atrophy F-box (MAFbx-1) in the rectus femoris. Compared with those of Group C, in Groups I and U, total contracture, myogenic contracture, MyoD and MAFbx-1 levels were significantly elevated, and CSA was significantly smaller (p < 0.05). Compared with those of Group I at each time point, MyoD levels were significantly elevated, MAFbx-1 levels were significantly lower, CSA was significantly larger, and myogenic contracture was significantly alleviated in Group U (p < 0.05). In the early stages of contracture, ultrashort wave diathermy reduces muscle atrophy and delays the process of myogenic contracture during joint immobilization; the mechanism of this may be explained as increased expression of MyoD triggered by suppression of the MAFbx-1-mediated ubiquitin-proteasome pathway.

Effect of Radial Extracorporeal Shock Wave Combined With Ultrashort Wave Diathermy on Fibrosis and Contracture of Muscle.

OBJECTIVE: The purpose of this study was to examine the intervention effect of radial extracorporeal shock wave combined with ultrashort wave diathermy on immobilization-induced fibrosis and contracture of muscle. DESIGN: The groups included male rabbits for the group (control group). To cause joint contracture, rabbits underwent plaster fixation of a left knee joint at full extension. After immobilization for 4 wks, all rabbits were randomly divided into five groups: model group, natural recovery group, radial extracorporeal shock wave treatment group, ultrashort wave diathermy group, and radial extracorporeal shock wave combined with ultrashort wave diathermy group. All intervention effects were assessed by evaluating the cross-sectional area and the collagen deposition of muscle, the knee joint range of motion and the protein levels for transforming growth factor ß1 and hypoxia-inducible factor 1α. RESULTS: The combined treatment group got the best recovery of the knee joint function. The combined treatment was more effective than radial extracorporeal shock wave or ultrashort wave diathermy alone against the fibrosis and contracture of muscle, as well as the overexpression of transforming growth factor ß1 and hypoxia-inducible factor 1α. CONCLUSIONS: Radial extracorporeal shock wave combined with ultrashort wave diathermy was effective in alleviating immobilization-induced contracture and fibrosis of muscle, as well as reducing the molecular manifestations of muscle fibrosis.

Environmental cadmium exposure during pregnancy causes diabetes-like phenotypes in mouse offspring: Association with oxidative stress in the fetal liver.

Cadmium (Cd), a noxious heavy metal, is widespread in the living environment. Gestational exposure to Cd at environmental dose has been shown to cause fetal growth restriction (FGR). However, the long-term effects and the mechanisms underlying environmental Cd exposure on glucose metabolism in offspring remain unclear. Here, we established a murine model to study the impacts of gestational exposure to environmental Cd on glucose metabolism at different life stages of offspring. Results demonstrated that the offspring mice developed hyperglycemia in puberty and impaired glucose tolerance in adulthood following maternal Cd exposure during gestation. Further mechanistic investigation showed that Cd exposure upregulated the expression of key proteins in hepatic gluconeogenesis, including p-CREB, PGC-1α and G6PC, in pubertal and adult offspring. In addition, we demonstrated that Cd exposure during pregnancy markedly elevated the level of oxidative stress-related proteins, including NOX2, NOX4 and HO-1, in the fetal liver. The effects of gestational exposure to N-acetylcysteine (NAC), a free-radical scavenging antioxidant, presented that NAC supplementation alleviated hepatic oxidative stress in fetuses, and thereby reversed hyperglycemia and glucose intolerance in mouse offspring. Collectively, our data suggested that gestational exposure to environmental Cd caused diabetes-like phenotypes via enhancing hepatic gluconeogenesis, which is associated with oxidative stress in fetal livers. This work provides new insights into the protective effects of antioxidants on fetal-originated diabetes triggered by environmental toxicants.

Effect of ultrashort wave treatment on joint dysfunction and muscle atrophy in a rabbit model of extending knee joint contracture: Enhanced expression of myogenic differentiation.

OBJECTIVE: To investigate the effects of ultrashort wave treatment on joint dysfunction and muscle atrophy in a rabbit model of extending knee joint contracture. METHODS: Forty rabbits were randomly divided into eight groups. In group C, the left knee joint was not fixed. In group I-8, the left knee joint was only fixed for eight weeks. In groups R-1, R-2, and R-4, the left knee joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of self-recovery, respectively. In groups T-1, T-2, and T-4, the left knee joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of ultrashort wave treatment, respectively. The degree of total contracture and myogenic contracture were measured, the cross-sectional area (CSA) and protein levels for myogenic differentiation (MyoD) of the rectus femoris were evaluated. RESULTS: There was a tendency toward a reduced degree of total and myogenic contracture, and also a tendency toward an increased CSA of the rectus femoris and increased protein levels for MyoD after both self-recovery and ultrashort wave treatment. The ultrashort wave was more effective than self-recovery in reducing the total and myogenic contracture, and increasing the CSA and MyoD protein levels of the rectus femoris. CONCLUSIONS: Ultrashort wave treatment may ameliorate joint dysfunction and muscle atrophy by upregulating the expression of MyoD protein in a rabbit model of extending knee joint contracture.