Use-dependent plasticity in spinal stepping and standing.
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Animals↗
Biomedical subjects
R R Roy
Publications and source records attributed to R R Roy.
Influence of two weeks of non-weight bearing on rat soleus motoneurons and muscle fibers.
BACKGROUND: Chronic unloading of the hindlimbs of rats results in atrophy and a shift in the metabolic and mechanical properties of the soleus muscle a predominantly slow postural muscle, towards those observed in faster muscles. HYPOTHESIS: We hypothesized that the spinal motoneurons innervating the soleus muscle would also atrophy and show adaptations in their metabolic properties following a period of unloading. METHODS: For 2 weeks, 10-week-old male Wistar rats were hindlimb suspended and the mean soma size and succinate dehydrogenase activity of motoneurons innervating the soleus muscle were examined. Retrograde labeling with nuclear yellow injected in the soleus muscle was used to identify the soleus motor pool. The mean fiber size and fiber type distribution from a central region of each soleus muscle was determined. RESULTS: The soma size distribution, mean soma cross-sectional area and mean succinate dehydrogenase activity of motoneurons in the soleus motor pool were similar in control and hindlimb suspended rats. In contrast, compared to control the mean fiber size of each fiber type and the percentages of Type I fibers decreased and of Type IIa fibers increased in the soleus muscle following hindlimb suspension. CONCLUSIONS: The results indicate that significant alterations in the phenotype and size of muscle fibers can occur without concomitant adaptations in the innervating motoneurons usually associated with motor unit types (i.e., soma size and oxidative capacity).
Analysis of Variance↗
Myosin heavy chain composition of adult feline (Felis catus) limb and diaphragm muscles.
The myosin heavy chain (MHC) compositions of adult feline limb and diaphragm muscles were determined. Sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) were able to separate three different MHC isoforms. This was in contrast to rat muscles, in which four MHC isoforms were separated by SDS-PAGE. The fastest migrating cat MHC migrated similar to rat type I MHC and labeled in Western blots with a monoclonal antibody (mAb) specific for slow MHC and was categorized as type I. The other two MHC isoforms labeled in Western blots with a mAb specific for fast MHC and were categorized as type II. The slowest migrating fast isoform migrated similar to rat type IIa MHC and labeled with mAb N2.261, specific for types I and IIa; therefore, this MHC was categorized as type IIa. The intermediate migrating cat MHC did not migrate similar to either rat type IIx or type IIb and was not reactive with mAbs N2.261, 35 (specific for rat I, IIa, and IIb MHCs), or F3 (specific for rat IIb MHC). In tissue sections, type IIB fibers (based on myofibrillar ATPase histochemistry) were also unstained with mAbs N2.261 and 35. Therefore, the intermediate migrating cat MHC was categorized as type IIx. Consequently, feline limb and diaphragm muscles were composed of fibers containing type I, IIa, or IIx MHCs. The observations that type I and IIa isoforms, but not IIx, had similar electrophoretic mobilities in the cat and rat and that type IIb was absent from cat limb muscles suggest that there is greater diversity in MHC isoforms IIb and IIx compared to I and IIa in cats compared to rats.
Animals↗
Comparison of succinate dehydrogenase activity and soma size relationships among neurons in dorsal root ganglia of rats and cats.
Compared to dorsal root ganglion (DRG) neurons at L5 in rats, DRG neurons at L7 in cat have a larger mean soma size, a bimodal rather than unimodal distribution of sizes and lower succinate dehydrogenase (SDH) activities for neurons of all sizes. In contrast to spinal motoneurons in both cats and rats, the larger DRG neurons have the higher SDH activities. The 10-20% higher SDH activity of DRG cells in rats than in cats may reflect, in part, a species difference of about 40% in metabolic rates.
Animals↗
Neural influence on slow muscle properties: inactivity with and without cross-reinnervation.
The effects of altering (cross-reinnervation, CR) and/or eliminating (spinal isolation, SI) the activation-dependent neural input to the cat soleus for 8 months on its mechanical and biochemical properties were determined. The percent fast fibers was 0, 27, 38, and 54% for normal control (NC), NC-CR, SI, and SI-CR cats. Calcium-activated whole muscle myofibrillar adenosine triphosphatase activity was higher in SI-CR and NC cats. Isometric twitch speed properties and frequency of stimulation:tension response were faster in all experimental groups compared to NC. Maximum twitch and tetanic (Po) force, physiological cross-sectional area (PCSA), and specific tension (Po/PCSA) were unaffected in NC-CR cats, but reduced in SI and SI-CR cats. The soleus was more fatigable in SI-CR compared to NC cats. Alpha-glycerophosphate dehydrogenase activity was higher in all experimental groups compared to NC. All eight parameters reflecting the type of muscle were shifted toward those observed in a "faster" muscle in SI-CR vs. SI cats. These data suggest that electrically silent motoneurons can influence type-related skeletal muscle properties.
Animals↗
Limited fiber type grouping in self-reinnervation cat tibialis anterior muscles.
The percent and distribution patterns of three immunohistochemically identified fiber types within the anterior compartment of the cat tibialis anterior were determined 6 months after denervation and self-reinnervation. After self-reinnervation, mean frequencies of slow (9%) and fast (91%) fibers were similar to those in control (12% and 88%, respectively) muscles. However, a lower proportion of fast-1 (26%) and a higher proportion of fast-2 (65%) fibers were observed in self-reinnervated than control (32% and 56%) muscles. Quantitation of adjacencies between fibers of similar myosin heavy chain (MHC) phenotype, a measure of type grouping, revealed that the frequencies of two slow or two fast-1 fibers being adjacent in self-reinnervated muscles were similar to control. In contrast, the frequency of fast-2/fast-2 fiber adjacencies found in self-reinnervated muscles (45%) was significantly higher than in control muscles (37%). In both groups, the frequency of adjacencies between slow, fast-1, or fast-2 fibers was largely attributable to the number of each fiber type present. These data show that the incidence of grouping within each fiber type present was not altered after 6 months of self-reinnervation. Minimal changes in the spatial distribution of fiber types following self-reinnervation in adults suggests a limited degree of conversion of muscle fibers to a MHC phenotype matching the motoneuron characteristics.
Animals↗
Myosin heavy chain profile of cat soleus following chronic reduced activity or inactivity.
To determine the role that normal neuromuscular activity plays in maintaining the myosin heavy chain (MHC) profile of adult cat soleus muscles, the spinal cords of 4 cats were transected (ST) and 8 cats were spinal isolated (SI) for 6 months. Nine nonoperated cats served as controls. Electrophoresis demonstrated that the soleus from control cats contained 98% type I, and 2% IIa MHCs. Both ST and SI resulted in decreased type I and increased IIa MHC, as well as de novo expression of IIb MHC. Immunohistochemistry with MHC-specific antibodies demonstrated that the soleus from control cats contained 99% type I, 1% IIa, and < 1% hybrid fibers (containing both type I and II MHCs). Following ST there were 67% type I, 17% IIa, 3% IIb, and 13% hybrid fibers. After SI, 48% of the fibers were type I, 11% were IIa, 1% were IIb, 25% were hybrid, and 15% contained embryonic MHC. Thus, normal levels of neuromuscular activity appear to be necessary for maintenance of the normal adult MHC profile in some fibers. Complete inactivation results in developmental MHC isoform expression in some fibers. Therefore, the dependence of a fiber on activity as a source of MHC modulation differs substantially among fibers even in a relatively homogeneous muscle.
Animals↗
Synergistic ablation does not affect atrophy or altered myosin heavy chain expression in the non-weight bearing soleus muscle.
The purpose of this study was to investigate whether the soleus muscle undergoes atrophy and alterations in myosin heavy chain (MHC) composition during non-weight bearing in the absence of synergists. Thirty-two female rats were randomly assigned to four groups: control (C), synergistic ablation (ABL) of the gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb suspension (HLS), or a combination of synergistic ablation and hindlimb suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non-weight bearing decreased mixed and myofibrillar protein contents and Type I MHC 49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS animals. Similarly, when compared to C rats, mixed and myofibrillar protein contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed. Collectively, these data indicate that the loss of muscle protein and Type I MHC, and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur independently of the presence of synergists during non-weight bearing. Furthermore, these results confirm the contention that soleus mass and MHC expression are highly sensitive to alterations in mechanical load.
Animals↗
Theoretical basis for patterning EMG amplitudes to assess muscle dysfunction.
A theoretical basis for assessing muscle dysfunction due to sprain/strain injuries is presented. We propose that muscle tissue trauma results in an alteration in the patterns of neural recruitment, a reduction in the force-generating capability of the injured muscle, and/or pain sensations. Furthermore, a lower than normal recruitment of motoneuron pools in the injured area can result in elevated recruitment levels from compensating motoneuron pools for a given motor task. It is proposed that these changes in motoneuron recruitment can be readily apparent in the ratios of EMG amplitudes among multiple pairs of muscles associated kinoffologically with the affected muscle. Chronic compensating actions, such as those resulting from faulty neural feedback of the force-length-velocity relationships for a stretched tendon or muscle unit, could cause further injuries. It is proposed that consistent and valid measures of ratios of EMG amplitudes between many muscle pairs acquired for well-defined motor tasks can be used to facilitate diagnoses and direct treatment strategies for sprain/strain injuries and pain.
Back↗
Specific tension of human plantar flexors and dorsiflexors.
Reported specific tension measurements for human skeletal muscle vary widely. This variability could be due, at least in part, to the determination of the physiological cross-sectional area (PCSA) of the muscles. In the present study, serial magnetic resonance images were taken every 10 mm along the lower leg of 8 male subjects to calculate the volume and subsequently the PCSAs of the individual muscles producing plantar flexor and dorsiflexor torques. Maximum plantar flexor and dorsiflexor voluntary isometric torques were determined at ankle joint angles of 90, 100, 110, and 120 degrees. Peak tendon force estimated from torque and moment arm measurements was more than fourfold higher in the plantar flexors (3,623 +/- 136 N) than in the dorsiflexors (832 +/- 19 N). PCSAs were about eight- and threefold higher than the anatomic cross-sectional areas at the level of maximum girth of the calf for the plantar flexor and dorsiflexor groups, respectively. Mean muscle volume and PCSA were 4.6 and 12 times larger in the plantar flexors compared with the dorsiflexors, respectively. The PCSAs of both plantar flexors (r = 0.92) and dorsiflexors (r = 0.80) were highly correlated with the tendon tension of the respective muscle groups. The maximum specific tension was more than twofold higher in dorsiflexors than in plantar flexors. These data suggest that factors other than PCSA contribute to the force output potential of ankle plantar flexors and dorsiflexors in humans.
Adult↗
MHC and sarcoplasmic reticulum protein isoforms in functionally overloaded cat plantaris muscle fibers.
To determine whether the adaptations in myosin heavy chain (MHC) isoform expression after functional overload (FO) are accompanied by commensurate adaptations in protein isoforms responsible for relaxation [sarco(endo)plasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (SERCA) and phospholamban (PHL)] in single muscle fibers, the isoforms of MHC and SERCA and the presence or absence of PHL were determined for cat plantaris fibers 3 mo after FO. In control plantaris the relative MHC isoform composition was 23% type I, 21% type IIa, and 56% type IIb. FO resulted in a shift toward slower isoforms (33% type I, 44% type IIa, and 23% type IIb). In the deep region of the plantaris the proportions of type I MHC and hybrid MHC fibers (containing type I and II MHCs) were 40 and 200% greater in FO cats, respectively. FO resulted in a 47% increase in the proportion of fibers containing only the slow SERCA isoform (SERCA2) and a 41% increase in the proportion of fibers containing PHL. The proportions of fibers containing type I MHC, SERCA2, and PHL in control and FO plantaris were linearly correlated. These data show that adaptations in MHC isoform expression are accompanied by commensurate adaptations in sarcoplasmic reticulum protein isoforms in single muscle fibers after FO.
Animals↗
Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight.
The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.
Animals↗
IGF-I, growth hormone, and/or exercise effects on non-weight-bearing soleus of hypophysectomized rats.
The effects of insulin-like growth factor (IGF-I) or growth hormone (GH) with and without exercise on predominantly slow muscles of hypophysectomized hindlimb-suspended (HS) rats were determined. HS resulted in a 21, 23, and 30% decrease in soleus, adductor longus, and vastus intermedius masses, respectively, compared with ambulatory rats. Compared with values in HS rats, IGF-I increased the vastus intermedius mass and GH or exercise alone increased both the soleus and vastus intermedius masses. There was a strong interactive effect between GH, but not IGF-I, and exercise in all three muscles of HS rats. The soleus fiber type distribution of HS rats was not affected by any treatment. HS resulted in a 24, 18 (P > 0.05), 32, and 20% (P > 0.05) decrease in the size of soleus fibers containing type I, IIa, I + IIa, and IIa + IIx myosin heavy chains, respectively, compared with ambulatory hypophysectomized rats. Hormone or exercise alone had no effect on fiber size in HS rats. However, all fiber sizes (except for type IIa + IIx in IGF-I with exercise rats) were larger in HS rats treated with GH or IGF-I and exercise than those in HS rats. These data indicate an interactive effect of both GH and IGF-I with exercise in maintaining fiber size of chronically non-weight-bearing predominantly slow muscles. Furthermore, the results suggest that the myosin heavy-chain phenotype in rats deficient in all pituitary factors is unresponsive to short-term administration of either GH or IGF-I or to exercise or HS.
Animals↗
Distribution of myosin heavy chain isoforms in non-weight-bearing rat soleus muscle fibers.
The effects of 14 days of spaceflight (SF) or hindlimb suspension (HS) (Cosmos 2044) on myosin heavy chain (MHC) isoform content of the rat soleus muscle and single muscle fibers were determined. On the basis of electrophoretic analyses, there was a de novo synthesis of type IIx MHC but no change in either type I or IIa MHC isoform proportions after either SF or HS compared with controls. The percentage of fibers containing only type I MHC decreased by 26 and 23%, and the percentage of fibers with multiple MHCs increased from 6% in controls to 32% in HS and 34% in SF rats. Type IIx MHC was always found in combination with another MHC or combination of MHCs; i.e., no fibers contained type IIx MHC exclusively. These data suggest that the expression of the normal complement of MHC isoforms in the adult rat soleus muscle is dependent, in part, on normal weight bearing and that the absence of weight bearing induces a shift toward type IIx MHC protein expression in the preexisting type I and IIa fibers of the soleus.
Animals↗
Skeletal muscle fiber cross-sectional area: effects of freezing procedures.
The cross-sectional area (CSA) of individual fibers is an important measure of skeletal muscle plasticity. To investigate the effects of different freezing procedures on CSA measurements, the CSA of type-identified fibers in the cat tibialis anterior were determined following quick-freezing the muscle at a fixed physiological length (ipsilateral, frozen at length) and compared to the fiber CSA following quick-freezing a mid-portion of the muscle where the fibers were allowed to freely shorten during tissue preparation (contralateral, frozen as a block). The mean CSA of each fiber type was significantly smaller in the muscles frozen at length vs. frozen as a block in both a deep (close to the bone) and a superficial (away from the bone) region of the muscle, except for the slow oxidative (SO) fibers in the superficial region. The percent difference in mean fiber CSA was smaller for the SO compared to the fast oxidative glycolytic and fast glycolytic fibers in both the deep (41, 47 and 56%, respectively) and superficial (20, 36 and 48%, respectively) regions. In addition, the differences in the mean CSAs of the fast fibers between the two freezing procedures were approximately 10% larger in the deep compared to the superficial region. The fiber-type differential responses may be related, at least in part, to the architectural features of the fibers. These data indicate that the freezing procedures used to prepare the muscle tissue are an important consideration when determining the CSA of individual skeletal muscle fibers and consequently the specific tension, tension per unit CSA, of the muscle units.
Animals↗
Influence of spaceflight on succinate dehydrogenase activity and soma size of rat ventral horn neurons.
Succinate dehydrogenase (SDH) activities and soma cross-sectional areas (CSA) of neurons in the dorsolateral region of the ventral horn at the L5 segmental level of the spinal cord in the rat were determined after 14 days of spaceflight and after 9 days of recovery on earth. The results were compared to those in age-matched ground-based control rats. Spinal cords were quick-frozen, and the SDH activity and CSA of a sample of neurons with a visible nucleus were determined using a digitizer and a computer-assisted image analysis system. An inverse relationship between CSA and SDH activity of neurons was observed in all groups of rats. No change in mean CSA or mean SDH activity or in the size distribution of neurons was observed following spaceflight or recovery. However, there was a selective decrease in the SDH activity of neurons with soma CSA between 500 and 800 microns2 in the flight rats, and this effect persisted for at least 9 days following return to 1 g. It remains to be determined whether the selected population of motoneurons or the specific motor pools affected by spaceflight may be restricted to specific muscles.
Animals↗
Recruitment of the Rhesus soleus and medial gastrocnemius before, during and after spaceflight.
Electromyograms were recorded from the soleus and medial gastrocnemius muscles and tendon force from the medial gastrocnemius muscle of 2 juvenile Rhesus monkeys before, during and after Cosmos flight 2229 and of ground control animals. Recording sessions were made while the Rhesus were performing a foot pedal motor task. Preflight testing indicated normal patterns of recruitment between the soleus and medial gastrocnemius, i.e. a higher level of recruitment of the soleus compared to the medial gastrocnemius during the task. Recording began two days into the spaceflight and showed that the media gastrocnemius was recruited preferentially over the soleus. This observation persisted throughout the flight and for the 2 week period of postflight testing. These data indicate a significant change in the relative recruitment of slow and fast extensor muscles under microgravity conditions. The appearance of clonic-like activity in one muscle of each Rhesus during flight further suggests a reorganization in the neuromotor system in a microgravity environment.
Animals↗
Response of the neuromuscular unit to spaceflight: what has been learned from the rat model.
Despite the inherent limitations placed on spaceflight investigations, much has been learned about the adaptations of the neuromuscular system to weightlessness from studies of rats flown for relatively short periods (approximately 4-22 days). Below is a summary of the major effects of spaceflight observed in muscles of rats that are not in their rapid growth stage: 1. Skeletal muscles atrophy rapidly during spaceflight; significant atrophy is observed as early as after 4 days of flight. 2. The atrophic response appears to be related to the primary function of the muscle. In the hindlimb, the relative amount of atrophy can be characterized as slow extensors > fast extensors > fast flexors. This pattern of relative atrophy does not appear to be occurring in the forelimb; however, not enough data are available to draw any definitive conclusions at this time. 3. Both slow and fast fibers atrophy during spaceflight, with the largest fibers within an individual muscle generally showing the greatest atrophic response. Interestingly, the amount of fiber atrophy appears to reach a plateau after about 14 days of flight. 4. Adaptations have been observed in the concentration and content of all muscle proteins pools, with the protein pools in slow muscles the most affected. 5. Some slow and fast fibers in predominantly slow and fast muscles show shifts in their histochemical and biochemical properties, toward those observed in a "faster" phenotype. 6. Some fibers, presumably expressing slow MHC isoforms before flight, begin to express fast MHC isoforms during flight. 7. The oxidative capacity of the muscles or fibers is relatively unaffected by spaceflight, particularly in the slow muscles. Any change in whole-body fatigability associated with spaceflight most likely reflects the loss in muscle and fiber mass. 8. The glycolytic capacity of the muscles and muscle fibers is enhanced after spaceflight. This metabolic adaptation seems to be related to the shift in the contractile proteins towards "faster" isoforms. 9. The vascularity of muscles appears to be maintained after flight, based, at least, on histological observations of capillarity. 10. The force capabilities of the muscles and fibers appear to decrease in parallel with the decreases in size, i.e., the specific tension is not significantly affected after flight. 11. Changes in the speed-related properties of the slow muscles are consistent with the adaptations in the myosin molecule, i.e., the slow muscles and some fibers in the slow muscles become "faster." 12. Some muscle fiber and neuromuscular junction damage has been observed after flight, particularly in the slow muscles. The extent of damage may be related to the amount of time that the muscles are allowed to reload before removal, i.e., in general, shorter intervals result in less fiber damage. 13. Adaptations in the motor (ventral horn) and sensory (spinal ganglia) neurons have been quite variable, but this may be related to the amount of time that the muscles are allowed to reload before removal. Morphological adaptations after relatively short periods of reloading may reflect a decrease in the activation of the neural elements during flight.
Adaptation, Physiological↗