Modulation of corticomotor excitability after maximal or sustainable-rate repetitive finger movement is impaired in Parkinson’s disease and is reversed by levodopa

Objectives: In healthy subjects, fatiguing exercises induce a period of post-exercise corticomotor depression (PECD) that is absent in Parkinson’s disease (PD). Our objective is to determine the time-course of corticomotor excitability changes following a 10-s repetitive index finger flexion–extension task performed at maximal voluntary rate (MVR) and a slower sustainable rate (MSR) in PD patients OFF and ON levodopa.
Methods: In 11 PD patients and 10 healthy age-matched controls, motor evoked potentials (MEPs) were recorded from the extensor indicis proprius (EIP) and first dorsal interosseous (FDI) muscles of the dominant arm immediately after the two tasks and at 2-min intervals for 10 min.
Results: In the OFF condition the PECD was absent in the two test muscles after both the MVR and MSR tasks. In the ON condition finger movement kinematics improved and a period of PECD comparable to that in controls was present after both tasks.
Conclusion: The absence of PECD in PD subjects off medication indicates a persisting increase in corticomotor excitability after non-fatiguing repetitive finger movement that is reversed by levodopa.

Are unilateral and bilateral patellar tendinopathy distinguished by differences in anthropometry, body composition, or muscle strength in elite female basketball players?

Background: Overuse injury to the patellar tendon (patellar tendinopathy) is a major reason for interrupted training and competition for elite athletes. In both sexes, the prevalence of unilateral and bilateral tendinopathy has been shown to differ. It has been proposed that bilateral pathology may have a different aetiology from unilateral pathology. Investigation of risk factors that may be unique to unilateral and bilateral patellar tendinopathy in female athletes may reveal insights into the aetiology of this condition.
Objectives: To examine whether anthropometry, body composition, or muscle strength distinguished elite female basketball players with unilateral or bilateral patellar tendinopathy.
Methods: Body composition, anthropometry, and muscle strength were compared in elite female basketball players with unilateral (n = 8), bilateral (n = 7), or no (n = 24) patellar tendinopathy. Body composition was analysed using a dual energy x ray absorptiometer. Anthropometric measures were assessed using standard techniques. Knee extensor strength was measured at 180°/s using an isokinetic dynamometer. z scores were calculated for the unilateral and bilateral groups (using the no tendinopathy group as controls). z scores were tested against zero.
Results: The tibia length to stature ratio was approximately 1.3 (1.3) SDs above zero in both the affected and non-affected legs in the unilateral group (p<0.05). The waist to hip ratio was 0.66 (0.78) SD above zero in the unilateral group (p<0.05). In the unilateral group, leg lean to total lean ratio was 0.42 (0.55) SD above zero (p<0.07), the trunk lean to total lean ratio was 0.63 (0.68) SD below zero (p<0.05), and leg fat relative to total fat was 0.47 (0.65) SD below zero (p<0.09). In the unilateral group, the leg with pathology was 0.78 (1.03) SD weaker during eccentric contractions (p<0.07).
Conclusions: Unilateral patellar tendinopathy has identifiable risk factors whereas bilateral patellar tendinopathy may not. This suggests that the aetiology of these conditions may be different. However, interpretation must respect the limitation of small subject numbers.

Interaction of exercise and diet on GLUT-4 protein and gene expression in type I and type II rat skeletal muscle

We determined the interaction of exercise and diet on glucose transporter (GLUT-4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty-eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high-fat (FAT, n =24) or high-carbohydrate (CHO, n =24). Animals in each dietary condition were allocated to one of two groups: control (NT, n =8) or a group that performed 8 weeks of treadmill running (4 sessions week^–1 of 1000 m @ 28 m min^–1 , RUN, n =16). Eight trained rats were killed after their final exercise bout for determination of GLUT-4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT-4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT-4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet–training interaction on GLUT-4 mRNA, such that expression was increased in both the soleus (100% ↑P < 0.05) and EDL (142% ↑P < 0.01) in CHO-fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL (↓ 45%, P < 0.05) but not the soleus (↓ 14%, NS). We conclude that exercise training in CHO-fed rats increased both GLUT-4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT-4 mRNA in muscles from fat-fed animals, exercise-induced increases in GLUT-4 protein were largely preserved, suggesting that control of GLUT-4 protein and gene expression are modified independently by exercise and diet.

Intense exercise up-regulates Na+, K+ -ATPase isoform mRNA, but not protein expression in human skeletal muscle

Characterization of expression of, and consequently also the acute exercise effects on, Na+,K+-ATPase isoforms in human skeletal muscle remains incomplete and was therefore investigated. Fifteen healthy subjects (eight males, seven females) performed fatiguing, knee extensor exercise at 40% of their maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue and 3 and 24 h postexercise, and analysed for Na+,K+-ATPase 1, 2, 3, ß1, ß2 and ß3 mRNA and crude homogenate protein expression, using Real-Time RT-PCR and immunoblotting, respectively. Each individual expressed gene transcripts and protein bands for each Na+,K+-ATPase isoform. Each isoform was also expressed in a primary human skeletal muscle cell culture. Intense exercise (352 ± 69 s; mean ±S.E.M.) immediately increased 3 and ß2 mRNA by 2.4- and 1.7-fold, respectively (P < 0.05), whilst 1 and 2 mRNA were increased by 2.5- and 3.5-fold at 24 h and 3 h postexercise, respectively (P < 0.05). No significant change occurred for ß1 and ß3 mRNA, reflecting variable time-dependent responses. When the average postexercise value was contrasted to rest, mRNA increased for 1, 2, 3, ß1, ß2 and ß3 isoforms, by 1.4-, 2.2-, 1.4-, 1.1-, 1.0- and 1.0-fold, respectively (P < 0.05). However, exercise did not alter the protein abundance of the 1–3 and ß1–ß3 isoforms. Thus, human skeletal muscle expresses each of the Na+,K+-ATPase 1, 2, 3, ß1, ß2 and ß3 isoforms, evidenced at both transcription and protein levels. Whilst brief exercise increased Na+,K+-ATPase isoform mRNA expression, there was no effect on isoform protein expression, suggesting that the exercise challenge was insufficient for muscle Na+,K+-ATPase up-regulation.

Depressed Na+-K+-ATPase activity in skeletal muscle at fatigue is correlated with increased Na+-K+-ATPase mRNA expression following intense exercise

We investigated whether depressed muscle Na⁺-K⁺-ATPase activity with exercise reflected a loss of Na⁺-K⁺-ATPase units, the time course of its recovery postexercise, and whether this depressed activity was related to increased Na⁺-K⁺-ATPase isoform gene expression. Fifteen subjects performed fatiguing, knee extensor exercise at ~40% maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue, 3 h, and 24 h postexercise and analyzed for maximal Na⁺-K⁺-ATPase activity via 3-O-methylfluorescein phosphatase (3-O-MFPase) activity, Na⁺-K⁺-ATPase content via [3H]ouabain binding sites, and Na⁺-K⁺-ATPase α1-, α2-, α3-, ß1-, ß2- and ß3-isoform mRNA expression by real-time RT-PCR. Exercise [352 (SD 267) s] did not affect [³H]ouabain binding sites but decreased 3-O-MFPase activity by 10.7 (SD 8)% (P < 0.05), which had recovered by 3 h postexercise, without further change at 24 h. Exercise elevated α1-isoform mRNA by 1.5-fold at fatigue (P < 0.05). This increase was inversely correlated with the percent change in 3-O-MFPase activity from rest to fatigue (%Δ3-O-MFPaserest-fatigue) (r = –0.60, P < 0.05). The average postexercise (fatigue, 3 h, 24 h) {alpha}1-isoform mRNA was increased 1.4-fold (P < 0.05) and approached a significant inverse correlation with %Δ3-O-MFPaserest-fatigue (r = –0.56, P = 0.08). Exercise elevated α2-isoform mRNA at fatigue 2.5-fold (P < 0.05), which was inversely correlated with %Δ3-O-MFPaserest-fatigue (r = –0.60, P = 0.05). The average postexercise α2-isoform mRNA was increased 2.2-fold (P < 0.05) and was inversely correlated with the %Δ3-O-MFPaserest-fatigue (r = –0.68, P < 0.05). Nonsignificant correlations were found between %Δ3-O-MFPaserest-fatigue and other isoforms. Thus acute exercise transiently decreased Na^+-K⁺-ATPase activity, which was correlated with increased Na⁺-K⁺-ATPase gene expression. This suggests a possible signal-transduction role for depressed muscle Na⁺-K⁺-ATPase activity with exercise.

Alterations in the proportions of skeletal muscle proteins following a unilateral lesion to the substantia nigra pars compacta of rats

It is well established that mammalian skeletal muscles exhibit a considerable degree of plasticity and one of the main determining factors of this plasticity is the activity pattern and duration of motoneurone discharge. Lesions to the right substantia nigra pars compacta (SNpc) of six adult rats were made to determine whether altered output from the SNpc ultimately leads to a change in the expression of proteins in contralateral skeletal muscles. After 4 months, altered motor performance was identified by the administration of amphetamine. After 7 months, 30–70% of dopaminergic cells in the SNpc had been destroyed. The protein content of muscles was then quantified from densitometric scans of gels, and expressed as a % of the amount of actin (the protein used as a reference in this study). The lesion affected the expression of different protein isoforms in the fast- and slow-twitch muscles. In slow-twitch soleus muscles, the lesion decreased the proportion of α-tropomyosin and increased the proportion of β-tropomyosin. In the fast-twitch extensor digitorum longus muscles, the lesion increased the proportion of the fast isoform of troponin-T_1f, and decreased the proportions of the two isoforms of myosin light chain. This study establishes a connection between the chronic effects of a lesion to the SNpc, with a loss of dopaminergic neurones, impaired motor performance, and altered expression of proteins in skeletal muscle. The implication of these results is that the altered motor function observed in Parkinson’s disease may be associated with alterations to the expression of skeletal muscle proteins.

Age and walking speed effects on muscle recruitment in gait termination

During gait termination at normal walking speed, older adults more frequently employ two-step responses, increasing their stopping distance and stopping time more than younger controls. This study investigated ageing effects on lower limb muscle recruitment patterns during stopping at three walking speeds. Twelve young male (26±3.7 years, range 19–30) and 12 gender-matched older participants (72±4.3 years, range 65–82) terminated walking at normal, medium and maximum speed. A visual stopping stimulus was presented 10 ms following either left or right heel-contact with no stimulus (catch) on 30% of trials. Electromyographic (EMG) activity was recorded from the tibialis anterior (TA), soleus (SOL), biceps femoris (BF), vastus lateralis (VL) and gluteus medius (GM). Older males more frequently (46% of trials) took two-steps to stop than young males (20%). The stance leg muscles responded significantly faster than the swing leg, and with increased speed, fewer swing limb muscles contributed to stopping. Older males were slower to respond with the stance leg, at 215 ms following the stimulus compared with 176 ms for the younger group. They also recruited fewer swing leg muscles with less frequent activation of the soleus and gluteus medius. Failure to activate muscles would provide less extensor torque to maintain the centre of gravity anterior to the forward base of support. This would decrease the total force opposing horizontal velocity in order to bring the body to rest and, as a consequence, encourage an additional step prior to stopping.

Antioxidant treatment with N-acetylcysteine regulates mammalian skeletal muscle Na+-K+-ATPase ∝ gene expression during repeated contractions

Exercise increases Na+–K+ pump isoform gene expression and elevates muscle reactive oxygen species (ROS). We investigated whether enhanced ROS scavenging induced with the antioxidant N-acetylcysteine (NAC) blunted the increase in Na+–K+ pump mRNA during repeated contractions in human and rat muscle. In experiment 1, well-trained subjects received saline or NAC intravenously prior to and during 45 min cycling. Vastus lateralis muscle biopsies were taken pre-infusion and following exercise. In experiment 2, isolated rat extensor digitorum longus muscles were pre-incubated without or with 10 mm NAC and then rested or stimulated electrically at 60 Hz for 90 s. After 3 h recovery, muscles were frozen. In both experiments, the muscles were analysed for Na+–K+ pump α1, α2, α3, β1, β2 and β3 mRNA. In experiment 1, exercise increased α2 mRNA by 1.0-fold (P = 0.03), but α2 mRNA was reduced by 0.40-fold with NAC (P = 0.03). Exercise increased α3, β1 and β2 mRNA by 2.0- to 3.4-fold (P < 0.05), but these were not affected by NAC (P > 0.32). Neither exercise nor NAC altered α1 or β3 mRNA (P > 0.31). In experiment 2, electrical stimulation increased α1, α2 and α3 mRNA by 2.3- to 17.4-fold (P < 0.05), but these changes were abolished by NAC (P > 0.07). Electrical stimulation almost completely reduced β1 mRNA but only in the presence of NAC (P < 0.01). Neither electrical stimulation nor NAC altered β2 or β3 mRNA (P > 0.09). In conclusion, NAC attenuated the increase in Na+–K+ pump α2 mRNA with exercise in human muscle and all α isoforms with electrical stimulation in rat muscle. This indicates a regulatory role for ROS in Na+–K+ pump α isoform mRNA in mammalian muscle during repeated contractions.

Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no L-NAME ingestion and acute exercise, rest plus L-NAME, and rest without L-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly (P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-{gamma} coactivator 1beta (PGC-1beta) mRNA levels and tended (P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or beta-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-{gamma} coactivator 1{alpha} (PGC-1{alpha}) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

Stimulation of calcineurin Aα activity attenuates muscle pathophysiology in mdx dystrophic mice

Calcineurin activation ameliorates the dystrophic pathology of hindlimb muscles in mdx mice and decreases their susceptibility to contraction damage. In mdx mice, the diaphragm is more severely affected than hindlimb muscles and more representative of Duchenne muscular dystrophy. The constitutively active calcineurin A transgene (CnA) was overexpressed in skeletal muscles of mdx (mdx CnA*) mice to test whether muscle morphology and function would be improved. Contractile function of diaphragm strips and extensor digitorum longus and soleus muscles from adult mdx CnA* and mdx mice was examined in vitro. Hindlimb muscles from mdx CnA* mice had a prolonged twitch time course and were more resistant to fatigue. Because of a slower phenotype and a decrease in fiber cross-sectional area, normalized force was lower in fast- and slow-twitch muscles of mdx CnA* than mdx mice. In the diaphragm, despite a slower phenotype and a 35% reduction in fiber size, normalized force was preserved. This was likely mediated by the reduction in the area of the diaphragm undergoing degeneration (i.e., mononuclear cell and connective and adipose tissue infiltration). The proportion of centrally nucleated fibers was reduced in mdx CnA* compared with mdx mice, indicative of improved myofiber viability. In hindlimb muscles of mdx mice, calcineurin activation increased expression of markers of regeneration, particularly developmental myosin heavy chain isoform and myocyte enhancer factor 2A. Thus activation of the calcineurin signal transduction pathway has potential to ameliorate the mdx pathophysiology, especially in the diaphragm, through its effects on muscle degeneration and regeneration and endurance capacity.

Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration

Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca²⁺- and Sr²⁺-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had ∼10% of the maximal force producing capacity (P_o) of control (uninjured) fibres, and an altered sensitivity to Ca²⁺ and Sr²⁺ at 7 days post-injury. Increased force production and a shift in Ca²⁺ sensitivity consistent with fibre maturation were observed during regeneration such that P_o was restored to 36–45% of that in control fibres by 21 days, and sensitivity to Ca²⁺ and Sr²⁺ was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed.

Effects of a daily school based physical activity intervention program on muscle development in prepubertal girls

This 12-month prospective controlled intervention evaluated the effect of a general school based physical activity program on muscle strength, physical performance and body composition in prepubertal girls. Fifty-three girls aged 7–9 years involved in a school based exercise program [40 min/day of general physical activity per school day (200 min/week)] were compared with 50 age-matched girls who participated in the general Swedish physical education curriculum (mean 60 min/week). Body composition (DXA), isokinetic peak torque (PT) of the knee extensors and flexors at 60 and 180°/s, and vertical jump height (VJH) were assessed at baseline and 12 months. The annual gain in weight was similar between the groups, but there was a greater increase in total body and regional lean mass (P < 0.05) and fat mass (P < 0.01) in the exercise group. Mean gains in knee extensor PT at 60 and 180°/s were 7.0–7.6% greater in the exercise group (P ranging <0.05–<0.001). No significant differences were detected in VJH. In conclusion, increasing school based physical education to at least 3 h/week provides a feasible strategy to enhance the development of muscle strength and lean mass in prepubertal girls.

Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification

A key regulatory point in the control of fatty acid (FA) oxidation is thought to be transport of FAs across the mitochondrial membrane by carnitine palmitoyltransferase I (CPT I). To investigate the role of CPT I in FA metabolism, we used in vivo electrotransfer (IVE) to locally overexpress CPT I in muscle of rodents. A vector expressing the human muscle isoform of CPT I was electrotransferred into the right lateral muscles of the distal hindlimb [tibialis cranialis (TC) and extensor digitorum longus (EDL)] of rats, and a control vector expressing GFP was electrotransferred into the left muscles. Initial studies showed that CPT I protein expression peaked 7 days after IVE (+104%, P < 0.01). This was associated with an increase in maximal CPT I activity (+30%, P < 0.001) and a similar increase in palmitoyl-CoA oxidation (+24%; P < 0.001) in isolated mitochondria from the TC. Importantly, oxidation of the medium-chain FA octanoyl-CoA and CPT I sensitivity to inhibition by malonyl-CoA were not altered by CPT I overexpression. FA oxidation in isolated EDL muscle strips was increased with CPT I overexpression (+28%, P < 0.01), whereas FA incorporation into the muscle triacylglycerol (TAG) pool was reduced (−17%, P < 0.01). As a result, intramyocellular TAG content was decreased with CPT I overexpression in both the TC (−25%, P < 0.05) and the EDL (−45%, P < 0.05). These studies demonstrate that acute overexpression of CPT I in muscle leads to a repartitioning of FAs away from esterification and toward oxidation and highlight the importance of CPT I in regulating muscle FA metabolism.

Resistive vibration exercise reduces lower limb muscle atrophy during 56-day bed-rest

OBJECTIVES: The current study aimed to examine the effectiveness of a resistive vibration exercise countermeasure during prolonged bed-rest in preventing lower-limb muscle atrophy. METHODS: 20 male subjects underwent 56-days of bed-rest and were assigned to either an inactive control, or a countermeasure group which performed high-load resistive exercises (including squats, heel raises and toe raises) with whole-body vibration. Magnetic resonance imaging of the lower-limbs was performed at two-weekly intervals. Volume of individual muscles was calculated. RESULTS: Countermeasure exercise reduced atrophy in the triceps surae and the vastii muscles (F>3.0, p<.025). Atrophy of the peroneals, tibialis posterior and toe flexors was less in the countermeasure-subjects, though statistical evidence for this was weak (F

Influence of vibration resistance training on knee extensor and plantar flexor size, strength, and contractile speed characteristics after 60 days of bed rest

Spaceflight and bed rest (BR) result in loss of muscle mass and strength. This study evaluated the effectiveness of resistance training and vibration-augmented resistance training to preserve thigh (quadriceps femoris) and calf (triceps surae) muscle cross-sectional area (CSA), isometric maximal voluntary contraction (MVC), isometric contractile speed, and neural activation (electromyogram) during 60 days of BR. Male subjects participating in the second Berlin Bed Rest Study underwent BR only [control (CTR), n = 9], BR with resistance training (RE; n = 7), or BR with vibration-augmented resistance training (RVE; n = 7). Training was performed three times per week. Thigh CSA and MVC torque decreased by 13.5 and 21.3%, respectively, for CTR (both P < 0.001), but were preserved for RE and RVE. Calf CSA declined for all groups, but more so (P < 0.001) for CTR (23.8%) than for RE (10.7%) and RVE (11.0%). Loss in calf MVC torque was greater (P < 0.05) for CTR (24.9%) than for RVE (12.3%), but not different from RE (14.8%). Neural activation at MVC remained unchanged in all groups. For indexes related to rate of torque development, countermeasure subjects were pooled into one resistance training group (RT, n = 14). Thigh maximal rate of torque development (MRTD) and contractile impulse remained unaltered for CTR, but MRTD decreased 16% for RT. Calf MRTD remained unaltered for both groups, whereas contractile impulse increased across groups (28.8%), despite suppression in peak electromyogram (12.1%). In conclusion, vibration exposure did not enhance the efficacy of resistance training to preserve thigh and calf neuromuscular function during BR, although sample size issues may have played a role. The exercise regimen maintained thigh size and MVC strength, but promoted a loss in contractile speed. Whereas contractile speed improved for the calf, the exercise regimen only partially preserved calf size and MVC strength. Modification of the exercise regimen seems warranted.