Effects of detraining on motor unit potential area,muscle function and physical performance based on CNTF gene polymorphism

[Purpose]

The purpose of this study was to identify the effect of detraining on motor unit potential area (SMUP), muscular function and physical performance, according to CNTF gene polymorphism.

[Methods]

For this study, GG (normal homozygote, n = 8) group and GA + AA (mutation heterozygote and homozygote, n = 10) group were divided by CNTF gene polymorphism and both groups were performed detraining for 4 weeks. The data was analyzed by two-way repeated measures ANOVA for verifying the differences between two groups and interaction using SPSS (ver. 20.0) statistical program.

[Results]

The results were as follows. First, changes in body composition were measured but there was no significant interaction effect between time and group. Seconds, changes in SMUP were measured by SEMG. Interaction effect between time and group was found lateral vastus during isokinetic exercise of 180°/sec (p < .05). Third, changes in isokinetic muscle strength of 60°/sec and 180°/sec were measured but there was no significant interaction effect. Fourth, significant statistical differences were not showed changes of sports performance after detraining.

[Conclusion]

In conclusion, there were no significantly differences between GG and GA + AA group after detraining, therefore, further study will be considered a matter in various its interventions such as serum levels of CNTF and changes in receptors and muscle fiber types.     

Cortical beta EEG oscillations related to changes in muscle tone activity during sleep in spider monkey (Ateles geoffroyi)

Background

The physiological mechanisms that allow for sleeping in a vertical position, which is primordial for arboreal primates, have not been studied yet.

Methods

A non‐invasive polysomnographic study of 6 spider monkeys (Ateles geoffroyi) was conducted. The relative beta power of the motor cortex and its linear relation with muscle tone in the facial mentalis muscle and the abductor caudae medialis muscle of the tail during wakefulness and sleep stages were calculated.

Results

A strong negative linear relationship (r = ?.8, P = .03) was found between the relative power of the beta2 band in the left motor cortex and abductor caudae medialis muscle tone during delta sleep.

Conclusions

The left motor cortex, through beta2 band activity, interacts with abductor caudae medialis muscle tonicity during delta sleep. This interaction takes part in the mechanisms that regulate the sleep postures.     

Age-Related Modifications to the Magnitude and Periodicity of Neuromuscular Noise

Background

Evaluation of task related outcomes within geriatric and fall-prone populations is essential not only for identification of neuromuscular deficits, but also for effective implementation of fall prevention strategies. As most tasks and activities of daily living are performed at submaximal force levels, restoration of muscle strength often does not produce the expected benefit in functional capacity. However, it is known that muscular control plays a key role in the performance of functional tasks, but it remains unclear to what degree muscular control and the associated neuromuscular noise (NmN) is age-related, particularly in the lower-extremities.

Objectives

The aim of this study was to determine the effects of age and fall-pathology on the magnitude as well as the frequency of NmN during lower extremity force production.

Methods

Sixteen young healthy adults, as well as seventy elderly women (36 healthy, 34 elderly fallers), performed force production tests at moderate levels (15% of maximum voluntary isometric contractions).

Results

Elderly fallers exhibited the highest magnitude of NmN, while the highest frequency components of NmN tended to occur in the healthy elderly. Young subjects exhibited significantly more power in the low frequency ranges than either of the elderly groups, and had the lowest levels of NmN.

Conclusion

These data suggest increased degeneration of muscular control through greater NmN in elderly fallers compared to healthy elderly or young subjects. This could possibly be associated with muscle atrophy and lower levels of motor unit synchronisation.     

A linear stochastic model of the single motor unit

The production of force and of the electrical signal by an active motor unit is theoretically described. Neural spikes are modelled using the Dirac delta function. Mechanisms for the generation of random impulse trains and the properties of the corresponding stochastic processes are discussed; the renewal model is proposed as the most appropriate. The possibility of using a linear model for the systems that produce force and electrical signal in the unit is examined. It is concluded that the linear assumption is justifiable during steady, constant-strength contractions of muscle. This linear stochastic model of the motor unit is used in two subsequent papers to study the muscle force and the electromyogram.     

Effects of mechanical assistance on muscle activity and motor performance during isometric elbow flexion

Mechanical assistance on joint movement is generally beneficial; however, its effects on cooperative performance and muscle activity needs to be further explored. This study examined how motor performance and muscle activity are altered when mechanical assistance is provided during isometric force control of ramp-down and hold phases. Thirteen right-handed participants (age: 24.7 ± 1.8 years) performed trajectory tracking tasks. Participants were asked to maintain the reference magnitude of 47 N (REF) during isometric elbow flexion. The force was released to a step-down magnitude of either 75% REF or 50% REF and maintained, with and without mechanical assistance. The ramp-down durations of force release were set to 0.5, 2.5, or 5.0 s. Throughout the experiment, we measured the following: (1) the force output using load cells to compute force variability and overshoot ratio; (2) peak perturbation on the elbow movement using an accelerometer; (3) the surface electromyography (sEMG) from biceps brachii and triceps brachii muscles; and (4) EMG oscillation from the biceps brachii muscle in the bandwidth of 15–45 Hz. Our results indicated that mechanical assistance, which involved greater peak perturbation, demonstrated lower force variability than non-assistance (p < 0.01), while EMG oscillation in the biceps brachii muscle from 15 to 45 Hz was increased (p < 0.05). These findings imply that if assistive force is provided during isometric force control, the central nervous system actively tries to stabilize motor performance by controlling specific motor unit activity in the agonist muscle.     

BDNF rescues myosin heavy chain IIB muscle fibers after neonatal nerve injury

Neonatal sciatic nerve injury is known to result in an extensive loss of lumbar motor neurons as well as the disappearance of their respective muscle fibers in the hindlimb musculature. The loss of motor neurons and muscle fibers can be prevented by immediate administration of target-derived neurotrophic factors to the site of injury. In the present study, we investigated the role of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the survival and maturation of a subset of motor neurons innervating the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles. We have shown that combined administration of CNTF and BDNF prevented the loss of motor units after neonatal nerve injury and contributed to the maintenance of muscle mass. Importantly, this combined neurotrophin regimen also prevented the disappearance of muscle fibers that express myosin heavy chain IIB (MyHC IIB) in both EDL and TA muscles 3 mo after neonatal sciatic nerve crush. In parallel studies, we observed a higher level of BDNF in EDL muscle during the critical period of development when motor neurons are highly susceptible to target removal. Given our previous findings that combined administration of CNTF with neurotrophin-3 (NT-3) or neurotrophin-4/5 (NT-4/5) did not result in the rescue of MyHC IIB fibers in EDL, the present results show the importance of muscle-derived BDNF in the survival and maturation of a subpopulation of motor neurons and of MyHC IIB muscle fibers during neonatal development of the neuromuscular system. motor neurons; neuromuscular development; neurotrophins     

Task-Dependent Intermuscular Motor Unit Synchronization between Medial and Lateral Vastii Muscles during Dynamic and Isometric Squats

Purpose

Motor unit activity is coordinated between many synergistic muscle pairs but the functional role of this coordination for the motor output is unclear. The purpose of this study was to investigate the short-term modality of coordinated motor unit activity–the synchronized discharge of individual motor units across muscles within time intervals of 5ms–for the Vastus Medialis (VM) and Lateralis (VL). Furthermore, we studied the task-dependency of intermuscular motor unit synchronization between VM and VL during static and dynamic squatting tasks to provide insight into its functional role.

Methods

Sixteen healthy male and female participants completed four tasks: Bipedal squats, single-leg squats, an isometric squat, and single-leg balance. Monopolar surface electromyography (EMG) was used to record motor unit activity of VM and VL. For each task, intermuscular motor unit synchronization was determined using a coherence analysis between the raw EMG signals of VM and VL and compared to a reference coherence calculated from two desynchronized EMG signals. The time shift between VM and VL EMG signals was estimated according to the slope of the coherence phase angle spectrum.

Results

For all tasks, except for singe-leg balance, coherence between 15–80Hz significantly exceeded the reference. The corresponding time shift between VM and VL was estimated as 4ms. Coherence between 30–60Hz was highest for the bipedal squat, followed by the single-leg squat and the isometric squat.

Conclusion

There is substantial short-term motor unit synchronization between VM and VL. Intermuscular motor unit synchronization is enhanced for contractions during dynamic activities, possibly to facilitate a more accurate control of the joint torque, and reduced during single-leg tasks that require balance control and thus, a more independent muscle function. It is proposed that the central nervous system scales the degree of intermuscular motor unit synchronization according to the requirements of the movement task at hand.     

The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

Objective

A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.

Methods

Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.

Results

Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.

Conclusion

The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.     

Simulation of motor unit recruitment and microvascular unit perfusion: spatial considerations

Fuglevand, Andrew J., and Steven S. Segal. Simulationof motor unit recruitment and microvascular unit perfusion: spatial considerations. J. Appl. Physiol.83(4): 1223-1234, 1997.Muscle fiber activity is the principalstimulus for increasing capillary perfusion during exercise. Thecontrol elements of perfusion, i.e., microvascular units (MVUs), supplyclusters of muscle fibers, whereas the control elements of contraction,i.e., motor units, are composed of fibers widely scattered throughoutmuscle. The purpose of this study was to examine how the discordantspatial domains of MVUs and motor units could influence the proportion of open capillaries (designated as perfusion) throughout a muscle crosssection. A computer model simulated the locations of perfused MVUs inresponse to the activation of up to 100 motor units in a muscle with40,000 fibers and a cross-sectional area of 100 mm². The simulation increasedcontraction intensity by progressive recruitment of motor units. Foreach step of motor unit recruitment, the percentage of active fibersand the number of perfused MVUs were determined for several conditions:1) motor unit fibers widely dispersed and motor unit territories randomly located (whichapproximates healthy human muscle),2) regionalized motor unitterritories, 3) reversed recruitmentorder of motor units, 4) denselyclustered motor unit fibers, and 5)increased size but decreased number of motor units. The simulationsindicated that the widespread dispersion of motor unit fibersfacilitates complete capillary (MVU) perfusion of muscle at low levelsof activity. The efficacy by which muscle fiber activity inducedperfusion was reduced 7- to 14-fold under conditions that decreased thedispersion of active fibers, increased the size of motor units, orreversed the sequence of motor unit recruitment. Such conditions aresimilar to those that arise in neuromuscular disorders, with aging, orduring electrical stimulation of muscle, respectively.

     

Genotyping and inflated type I error rate in genome-wide association case/control studies

Background  

One common goal of a case/control genome wide association study (GWAS) is to find SNPs associated with a disease. Traditionally, the first step in such studies is to assign a genotype to each SNP in each subject, based on a statistic summarizing fluorescence measurements. When the distributions of the summary statistics are not well separated by genotype, the act of genotype assignment can lead to more potential problems than acknowledged by the literature.     

No association between <Emphasis Type="Italic">NOS2</Emphasis> and <Emphasis Type="Italic">NOS3</Emphasis> polymorphisms and diabetic nephropathy in type 2 diabetics

Background  

Diabetic animal models suggest the involvement of nitric oxide (NO)-producing enzymes in the development of diabetic nephropathy (DN). While early stages of DN are associated with increased intrarenal NO, advanced DN is related to progressive NO deficiency. NO collaborates in reactive nitrogen compounds production, contributing to accelerated oxidative stress. To investigate the impact of genetic polymorphisms of NO-producing enzymes on DN development, we tested 3 polymorphic variants that could affect their function and compared genotype status to an oxidative stress marker.     

Assessment of precision and reproducibility of a new myograph

Background  

The physiological characteristics of muscle activity and the assessment of muscle strength represent important diagnostic information. There are many devices that measure muscle force in humans, but some require voluntary contractions, which are difficult to assess in weak or unconscious patients who are unable to complete a full range of voluntary force assessment tasks. Other devices, which obtain standard muscle contractions by electric stimulations, do not have the technology required to induce and measure reproducible valid contractions at the optimum muscle length.     

Neuromuscular drive and force production are not altered during bilateral contractions

Jakobi, J. M., and E. Cafarelli. Neuromuscular driveand force production are not altered during bilateral contractions. J. Appl. Physiol. 84(1): 200-206, 1998.Several investigators have studied the deficit in maximalvoluntary force that is said to occur when bilateral muscle groupscontract simultaneously. A true bilateral deficit (BLD) would suggest asignificant limitation of neuromuscular control; however, some of thedata from studies in the literature are equivocal. Our purpose was todetermine whether there is a BLD in the knee extensors of untrainedyoung male subjects during isometric contractions and whether thisdeficit is associated with a decreased activation of the quadriceps,increased activation of the antagonist muscle, or an alteration inmotor unit firing rates. Twenty subjects performed unilateral (UL) and bilateral (BL) isometric knee extensions at 25, 50, 75, and 100% maximal voluntary contraction. Total UL and BL force (3%) and maximal rate of force generation (2.5%) were not significantly different. Total UL and BL maximal vastus lateralis electromyographic activity (EMG; 2.7 ± 0.28 vs. 2.6 ± 0.24 mV) andcoactivation (0.17 ± 0.02 vs. 0.20 ± 0.02 mV) were also notdifferent. Similarly, the ratio of force to EMG during submaximal ULand BL contractions was not different. Analysis of force production byeach leg in UL and BL conditions showed no differences in force, rateof force generation, EMG, motor unit firing rates, and coactivation.Finally, assessment of quadriceps activity with the twitchinterpolation technique indicated no differences in the degree ofvoluntary muscle activation (UL: 93.6 ± 2.51 Hz, BL: 90.1 ± 2.43 Hz). These results provide no evidence of a significant limitationin neuromuscular control between BL and UL isometric contractions ofthe knee extensor muscles in young male subjects.

     

Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

Background

Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS.

Methodology/Principal Findings

We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model.

Conclusions/Significance

These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases.     

Evidence of Significant Central Fatigue in Patients with Cancer-Related Fatigue during Repetitive Elbow Flexions till Perceived Exhaustion

Objective

To investigate whether fatigue induced by an intermittent motor task in patients with cancer-related fatigue (CRF) is more central or peripheral.

Methods

Ten patients with CRF who were off chemo and radiation therapies and 14 age-matched healthy controls were enrolled. Participants completed a Brief Fatigue Inventory (BFI) and performed a fatigue task consisting of intermittent elbow-flexion contractions at submaximal (40% maximal voluntary contraction) intensity till self-perceived exhaustion. Twitch force was elicited by an electrical stimulation applied to the biceps brachii muscle. The relative degree of peripheral (muscle) vs. central contribution to fatigue induced by the intermittent motor task (IMT) was assessed using twitch force ratio (TF_ratio) defined as post IMT twitch force to pre IMT twitch force. The total number of trials (intermittent contractions) and total duration of all trials performed by each subject were also quantified.

Results

BFI scores were higher (p<0.001) in CRF than controls, indicating greater feeling of fatigue in CRF patients than controls. A significantly smaller number of trials and shorter total duration of the trials (p<0.05) were observed in CRF than control participants. The TF_ratio (0.81±0.05) in CRF was higher (p<0.05) compared with that of controls (0.62±0.05), suggesting CRF patients experienced a significantly lower degree of muscle (peripheral) fatigue at the time of perceived exhaustion.

Conclusion

Consistent with prior findings for fatigue under submaximal sustained contraction, our results indicate that motor fatigue in CRF is more of central than peripheral origin during IMT. Significant central fatigue in CRF patients limits their ability to prolong motor performance.     

Complex myograph allows the examination of complex muscle contractions for the assessment of muscle force, shortening, velocity, and work in vivo

Background

The devices used for in vivo examination of muscle contractions assess only pure force contractions and the so-called isokinetic contractions. In isokinetic experiments, the extremity and its muscle are artificially moved with constant velocity by the measuring device, while a tetanic contraction is induced in the muscle, either by electrical stimulation or by maximal voluntary activation. With these systems, experiments cannot be performed at pre-defined, constant muscle length, single contractions cannot be evaluated individually and the separate examination of the isometric and the isotonic components of single contractions is not possible.

Methods

The myograph presented in our study has two newly developed technical units, i.e. a). a counterforce unit which can load the muscle with an adjustable, but constant force and b). a length-adjusting unit which allows for both the stretching and the contraction length to be infinitely adjustable independently of one another. The two units support the examination of complex types of contraction and store the counterforce and length-adjusting settings, so that these conditions may be accurately reapplied in later sessions.

Results

The measurement examples presented show that the muscle can be brought to every possible pre-stretching length and that single isotonic or complex isometric-isotonic contractions may be performed at every length. The applied forces act during different phases of contraction, resulting into different pre- and after-loads that can be kept constant - uninfluenced by the contraction. Maximal values for force, shortening, velocity and work may be obtained for individual muscles. This offers the possibility to obtain information on the muscle status and to monitor its changes under non-invasive measurement conditions.

Conclusion

With the Complex Myograph, the whole spectrum of a muscle's mechanical characteristics may be assessed.     

Differential scanning calorimetry study of glycerinated rabbit psoas muscle fibres in intermediate state of ATP hydrolysis

Background  

Thermal denaturation experiments were extended to study the thermal behaviour of the main motor proteins (actin and myosin) in their native environment in striated muscle fibres. The interaction of actin with myosin in the highly organized muscle structure is affected by internal forces; therefore their altered conformation and interaction may differ from those obtained in solution. The energetics of long functioning intermediate states of ATP hydrolysis cycle was studied in muscle fibres by differential scanning calorimetry (DSC).     

CNTF Induces Regeneration of Cone Outer Segments in a Rat Model of Retinal Degeneration

Background

Cone photoreceptors are responsible for color and central vision. In the late stage of retinitis pigmentosa and in geographic atrophy associated with age-related macular degeneration, cone degeneration eventually causes loss of central vision. In the present work, we investigated cone degeneration secondary to rod loss in the S334ter-3 transgenic rats carrying the rhodopsin mutation S334ter.

Methodology/Principal Findings

Recombinant human ciliary neurotrophic factor (CNTF) was delivered by intravitreal injection to the left eye of an animal, and vehicle to the right eye. Eyes were harvested 10 days after injection. Cone outer segments (COS), and cell bodies were identified by staining with peanut agglutinin and cone arrestin antibodies in whole-mount retinas. For long-term treatment with CNTF, CNTF secreting microdevices were implanted into the left eyes at postnatal day (PD) 20 and control devices into the right eyes. Cone ERG was recorded at PD 160 from implanted animals. Our results demonstrate that an early sign of cone degeneration is the loss of COS, which concentrated in many small areas throughout the retina and is progressive with age. Treatment with CNTF induces regeneration of COS and thus reverses the degeneration process in early stages of cone degeneration. Sustained delivery of CNTF prevents cones from degeneration and helps them to maintain COS and light-sensing function.

Conclusions/Significance

Loss of COS is an early sign of secondary cone degeneration whereas cell death occurs much later. At early stages, degenerating cones are capable of regenerating outer segments, indicating the reversal of the degenerative process. Sustained delivery of CNTF preserves cone cells and their function. Long-term treatment with CNTF starting at early stages of degeneration could be a viable strategy for preservation of central vision for patients with retinal degenerations.