Short-time recovery skeletal muscle from dexamethasone-induced atrophy and weakness in old female rats.

BACKGROUND: Several pathological conditions (atrophy, dystrophy, spasticity, inflammation) can change muscle biomechanical parameters. Our previous works have shown that dexamethasone treatment changes skeletal muscle tone, stiffness, elasticity. Exercise training may oppose the side effects observed during dexamethasone treatment. The purpose of this study was to examine the changes in biomechanical parameters (tone, stiffness, elasticity) of skeletal muscle occurring during dexamethasone treatment and subsequent short-time recovery from glucocorticoid-induced muscle atrophy and weakness, as well as the effect of mild therapeutic exercise. METHODS: 17 old female rats, aged 22 months were used in this study. The hand-held and non-invasive device (MyotonPRO, Myoton Ltd., Tallinn, Estonia) was used to study changes in biomechanical properties of muscle. Additionally, body and muscle mass, hind limb grip strength were assessed. FINDINGS: Results showed that dexamethasone treatment alters muscle tone, stiffness and elasticity. During 20-day recovery period all measured parameters gradually improved towards the average baseline, however, remaining significantly lower than these values. The body and muscle mass, hind limb grip strength of the rats decreased considerably in the groups that received glucocorticoids. After 20 days of recovery, hind limb grip strength of the animals was slightly lower than the baseline value and mild therapeutic exercise had a slight but not significant effect on hind limb grip strength. Biomechanical parameters improved during the recovery period, but only dynamic stiffness and decrement retuned to baseline value. INTERPRETATION: The study results show that monitoring muscle biomechanical parameters allows to assess the recovery of atrophied muscle from steroid myopathy.

Changes in Body Composition of Old Rats at Different Time Points After Dexamethasone Administration.

BACKGROUND: Aging leads to changes in skeletal muscle quantity and quality and is accompanied with increase in body mass and fat mass, whereas fat-free mass either decreases or remains unchanged. The body composition of rodents has been an important factor for clinical trials in the laboratory. Glucocorticoids such as dexamethasone are widely used in clinical medicine, but may induce myopathy, characterized by muscle weakness, atrophy, and fatigue. In animals treated with glucocorticoids, a dose-dependent reduction of body weight has been observed. This weight loss is usually followed by muscle atrophy and a reduction of several muscle proteins, contributing to impaired muscle function. This study was designed to describe changes in body composition and BMC of 22-month-old rats during 10- and 20-day recovery period after 10-day dexamethasone administration. METHOD: Data on body mass, lean body mass, fat mass and bone mineral content of the rats were obtained with dual energy X-ray absorptiometry scan. RESULT: Significant reduction in body mass, lean body mass, fat mass and fast-twitch muscle mass was observed after dexamethasone treatment. Body mass, fat mass and fast-twitch muscle mass stayed decreased during 20 days after terminating the hormone administration; lean body mass reached the preadministration level after 20-day recovery period. There were no significant changes in bone mineral density during the recovery period. Dexamethasone treatment gradually reduced hindlimb grip strength that also stayed decreased during the 20-day recovery period. CONCLUSION: This study demonstrated that a 10-day period of overexprosure to glycocorticoids induced longlasting changes in old rats' body composition and these values did not attain the baseline level even after 20-day recovery period.

Glucocorticoid-Induced Changes in Rat Skeletal Muscle Biomechanical and Viscoelastic Properties: Aspects of Aging.

OBJECTIVES: The purpose of this study was to estimate the state of tension (tone) and the biomechanical and viscoelastic properties of skeletal muscle in aging rats during the administration of different doses of dexamethasone and to find the relationships among the state of muscle atrophy, muscle strength, and the abovementioned muscle properties. METHODS: Muscle state of tension, biomechanical (elasticity, dynamic stiffness) and viscoelastic (mechanical stress relaxation time, Deborah number) properties (using MyotonPRO, Myoton Ltd, Tallinn, Estonia), lean body mass (BM), and hind limb grip strength were measured before and after the administration of a 10-day treatment with dexamethasone 100 µg/100 g BM (young and old group) and 50 µg/100 g BM (old group). RESULTS: Muscle elasticity (logarithmic decrement) was lower in old animals (1.86 ± 0.03) in comparison with young adult rats (1.38 ± 0.04) (P < .01). After the 10-day treatment with dexamethasone 100 µg/100 g BM, young adult rats had 10% lower muscle elasticity (P < .01). The same dose of dexamethasone in old rats increased tone (frequency of natural oscillation) from 29.13 ± 0.51 Hz to 38.50 ± 0.95 Hz (P < .001). There were dose-dependent differences in dynamic stiffness and tone of muscle; changes in elasticity were independent of the dose in old animals. In old rats, the muscle's viscoelastic properties decreased after dexamethasone administration. Significant correlation was found between changes in muscle logarithmic decrement and stiffness (rs = 0.90; P < .05) in old animals. CONCLUSIONS: Biomechanical and viscoelastic properties of skeletal muscle indicate changes in the main function of muscle during glucocorticoid-induced muscle atrophy and are in agreement with changes in hind limb strength. The myometric measurements indicate the direction and magnitude of change in muscle tissue after different doses of dexamethasone administration easily and quickly.

Aging and regenerative capacity of skeletal muscle in rats.

The objective of the study was to examine skeletal muscle regeneration capacity of young and very old rats during autotransplantation. In 3.5 and 30 month-old Wistar rats, gastrocnemius muscle was removed and grafted back to its original bed. Incorporation of 3H leucine into myofibrillar and sarcoplasmic protein fractions, their relative contents in autografts and synthesis rate of MyHC and actin were recorded. The relative muscle mass of old rats was about 67% of that of young rats; the absolute mass of autografted muscle was 61% intact in the young rat group and 51% in the old rat group. Content of myofibrillar protein in the autografts of young rats was 46% of the intact muscle content, and 39% in the old rat group. In conclusion, the difference in skeletal muscle regeneration capacity of young and very old rats is about ten percent. In the autografts of both young and old rats, the regeneration of the contractile apparatus is less effective in comparison with the sarcoplasmic compartment.

Relationship between extracellular matrix, contractile apparatus, muscle mass and strength in case of glucocorticoid myopathy.

The purpose of this study was to evaluate the effect of dexamethasone on the contractile apparatus and extracellular matrix (ECM) components of slow-twitch (ST) soleus (Sol) and fast-twitch (FT) extensor digitorum longus (EDL) muscle. The specific aim was to assess the development of glucocorticoid-induced myopathy on the level of contractile apparatus and ECM, paying attention to the expression of fibrillar forming collagen types I and III and nonfibrillar type IV collagen expression in extracellular compartment of muscle. Degradation of myofibrillar proteins increased from 2.62+/-0.28 to 5.58+/-0.49% per day during glucocorticoids excess. Both fibril- and network-forming collagen-specific mRNA levels decreased at the same time in both types of skeletal muscle. Specific mRNA level for MMP-2 did not change significantly during dexamethasone administration. Hindlimb grip strength simultaneously decreased. The effect of excessive glucocorticoids on the extracellular compartment did not differ significantly in skeletal muscles with different twitch characteristics.

Ageing and dexamethasone associated sarcopenia: peculiarities of regeneration.

The purpose of this study was to assess the development of ageing- and glucocorticoid-related sarcopenia on the level of myofibrillar apparatus, paying attention to the synthesis (SR) and degradation rate (DR) of contractile proteins, muscle strength, and daily motor activity. We also wanted to test the effect of ageing and dexamethasone (Dex) excess on the regeneration peculiarities of skeletal muscle autografts. Four and 30-month-old male rats of the Wistar strain were used. Ageing associated sarcopenia was calculated from gastrocnemius muscle relative mass decrease (from 5.6 +/- 0.08 to 3.35 +/- 0.04; p < 0.001). The SR of MyHC in old rats was approximately 30% and actin approximately 23% lower than in young rats. Dex treatment decreased SR of two main contractile proteins significantly in both age groups (p < 0.001) and increased DR during ageing from 2.11 +/- 0.15 to 4.09 +/- 0.29%/day (p < 0.001). Hindlimb grip strength in young rats was 5.90 +/- 0.35 N/100 g bw and 2.64 +/- 0.2 N/100 g bw (p < 0.001) in old rats. Autografts of old rats have a higher content of adipose tissue 14.9 +/- 1.1% in comparison with young rats 6.8 +/- 0.51% (p < 0.001) and less muscle tissue 39.8 +/- 2.6% and 48.3 +/- 2.8%, respectively (p < 0.05). Both, ageing and dex-caused sarcopenic muscles have diminished capacity for regeneration.

Altered mitochondrial apparent affinity for ADP and impaired function of mitochondrial creatine kinase in gluteus medius of patients with hip osteoarthritis.

The cellular energy metabolism in human musculus gluteus medius (MGM) under normal conditions and hip osteoarthritis (OA) was explored. The functions of oxidative phosphorylation and energy transport systems were analyzed in permeabilized (skinned) muscle fibers by oxygraphy, in relation to myosin heavy chain (MHC) isoform distribution profile analyzed by SDS-PAGE, and to creatine kinase (CK) and adenylate kinase (AK) activities measured spectrophotometrically in the intact muscle. The results revealed high apparent Km for ADP in regulation of respiration that decreased after addition of creatine in MGM of traumatic patients (controls). OA was associated with increased sensitivity of mitochondrial respiration to ADP, decreased total activities of AK and CK with major reduction in mi-CK fraction, and attenuated effect of creatine on apparent Km for ADP compared with control group. It also included a complete loss of type II fibers in a subgroup of patients with the severest disease grade. It is concluded that energy metabolism in MGM cells is organized into functional complexes of mitochondria and ATPases. It is suggested that because of degenerative remodeling occurring during development of OA, these complexes become structurally and functionally impaired, which results in increased access of exogenous ADP to mitochondria and dysfunction of CK-phosphotransfer system.

Adaptive changes of Myosin isoforms in response to long-term strength and power training in middle-aged men.

The purpose of the study was to examine the adaptive changes in myosin heavy chain (MHC) and light chain (MLC) isoforms in human vastus lateralis muscle caused by long-term strength and power training (54 weeks, approximately 3 times a week) in untrained middle- aged men (16 in the training and 6 in the control group). Muscular MHC and MLC isoforms were determined by means of SDS-PAGE gel electrophoresis. During the training period, maximal anaerobic cycling power increased by 64 W (p < 0.001) and the maximal jumping height by 1.5 cm (p < 0. 05) in the training group, but no significant changes were found in the control group. However, the group by time effect was not significant. In the training group, the increase of the maximal jumping height correlated with the number of strength and power training sessions (r = 0.56; p < 0.05). The change of the proportion of MHC IIa isoform from 52.6 ± 12.2% to 59.4 ± 11.6% did not reach statistical significance (p = 0.070 for group by time; within training group p = 0.061) and neither did the change of the proportion of MHC IIx isoform from 18.1 ± 11.4% to 11.1 ± 9.1% (p = 0.104 for group by time; within training group p=0.032). The degree of change of MHC IIx isoform correlated with the amount of earlier recreational sports activity (r = 0.61; p < 0.05). In the training group, the changes of MLC1s isoform correlated negatively with the changes of MLC1f isoform (r = -0. 79; p < 0.05) as well as with the changes in maximal anaerobic cycling power (r = -0.81; p < 0.05), and positively with those of MHC I isoform (r = 0.81; p < 0.05). In conclusion, the long- term strength and power training ~3 times a week seemed to have only slight effects on fast MHC isoforms in the vastus lateralis muscle of untrained middle-aged men; the proportion of MHC IIa tended to increase and that of MHC IIx tended to decrease. No changes in MLC isoform profile could be shown. Key PointsA long-term strength and power training program seemed to decrease the proportion of MHC IIx isoform in previously untrained middle-aged men.The degree of change of MHC IIx isoform correlated with the amount of earlier recreational sports activity.The changes of MLC isoforms were associated with the transition of MHC isoforms. Whether this means improved speed and coordination of muscle contraction remains to be investigated in the future.

Age-related changes in skeletal-muscle myosin heavy-chain composition: effect of mechanical loading.

The purpose of this study was to investigate the effect of compensatory hypertrophy (CH), heavy-resistance exercise training (HRET), and simultaneous CH and HRET on fast-twitch skeletal-muscle myofibrillar-protein synthesis, myosin heavy-chain (MHC) turnover rate, and MHC-isoform composition in young and old rats. In young animals all treatments intensified myofibrillar-protein synthesis, whereas in old animals with CH protein synthesis remained unchanged. The relative content of MHC I and IID in plantaris muscle increases with age, and the relative content of MHC IIB decreases. HRET and simultaneous CH and HRET decreased the proportion of MHC IIB and IIA and increased that of MHC IID in young rat muscle. In old rat muscle, relative content of MHC IID decreased and that of MHC IIB increased. CH decreased relative content of MHC IIB in both age groups and of MHC IIA in old animals. Relative content of MHC IID increased in both groups, and of MHC IIA, in young animals. MHC in plantaris of young rats turned over much faster in all types of mechanical loading but in old rats only during HRET and its combination with CH.

The effect of glucocorticoids on the myosin heavy chain isoforms' turnover in skeletal muscle.

The purpose of this study was to find the effect of dexamethasone on the myosin heavy chain (MyHC) isoforms' composition in different skeletal muscles and glycolytic (G) fibres in relation with their synthesis rate and degradation of MyHC isoforms by alkaline proteinases. Eighteen-week-old male rats of the Wistar strain were treated with dexamethasone (100 microg/100 g bwt) during 10 days. The forelimb strength decreased from 9.52 to 6.19 N (P<0.001) and hindlimb strength from 15.54 to 8.55 N (P<0.001). Daily motor activity decreased (total activity from 933 to 559 and ambulatory activity from 482 to 226 movements/h, P<0.001). The degradation rate of muscle contractile proteins increased from 2.0 to 5.9% per day (P<0.001), as well as the myosin heavy chain IIB isoform degradation with alkaline proteinase in fast-twitch (F-T) muscles (12 +/- 0.9%; P<0.05) and glycolytic muscle fibres (15 +/- 1.1%; P<0.001). The synthesis rate of MyHC type II isoforms decreased in Pla muscles (P<0.05) and MyHC IIA (P<0.05) and IIB in EDL muscle and G fibres (P<0.001). The relative content of MyHC IIB isoform decreased in F-T muscles (P<0.001) and in G fibres (P<0.01), and the relative content of IIA and IID isoforms increased simultaneously. Dexamethasone decreased the MyHC IIB isoform synthesis rate and increased the sensibility of MyHC IIB isoform to alkaline proteinase, which in its turn led to the decrease of MyHC IIB isoform relative content in F-T muscles with low oxidative potential and G muscle fibres.