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R R Roy

Publications and source records attributed to R R Roy.

At least 145 records · Page 8Linked to original sources

Can the mammalian lumbar spinal cord learn a motor task?

Progress toward restoring locomotor function in low thoracic spinal transected cats and the application of similar techniques to patients with spinal cord injury is reviewed. Complete spinal cord transection (T12-T13) in adult cats results in an immediate loss of locomotor function in the hindlimbs. Limited locomotor function returns after several months in cats that have not received specific therapies designed to restore hindlimb stepping. Training transected cats to step on a treadmill for 30 min.d-1 and 5 d.wk-1 greatly improves their stepping ability. The most successful outcome was in cats where training began early, i.e., 1 wk after spinal transection. Cats trained to stand instead of stepping had great difficulty using the hindlimbs for locomotion. These effects were reversible over a 20-month period such that cats unable to step as a result of standing training could be trained to step and, conversely, locomotion in stepping-trained cats could be abolished by standing training. These results indicate that the spinal cord is capable of learning specific motor tasks. It has not been possible to elicit locomotion in patients with clinically complete spinal injuries, but appropriately coordinated EMG activity has been demonstrated in musculature of the legs during assisted locomotion on a treadmill.

Animals↗

The physiological cross-sectional area of motor units in the cat tibialis anterior.

The physiological cross-sectional area (CSA) of a motor unit (MU), taken as the sum of fiber areas measured on a single section through the approximate midlength of the MU, has been compared with the physiological CSA more strictly defined as the sum of the maximal areas to be found anywhere along the length of each of the MU fibers. The CSA at intervals along the fiber length was measured in fibers selected from four glycogen-depleted, isolated MUs in the cat tibialis anterior (TA), and profiles of the summed areas made. In one MU, measurements were also taken on all the MU's fibers at less frequent intervals. The profiles demonstrate that the summed CSA based on each fiber's maximum CSA may exceed that derived from observation on any single section by as much as 20%. As a consequence, values that have been reported for specific tension (force per unit area) of MUs in the TA and probably other muscles may have been overestimated, especially for those MUs of fast type. Estimates were also made of the share of the MU's total force transmitted directly to the tendons of origin and insertion via endings of the blunt musculotendinous type as distinct from tapering intrafascicular endings acting through in-series connective tissue and non-MU fibers. In two MUs of slow type in which most fibers ran from tendon to tendon, "partial tapering" extending over 1 cm of the fiber length accounted for a third of the total physiological CSA, and indicated yet another mode for relay of the MU's force to the tendon.

Animals↗

Tapering of the intrafascicular endings of muscle fibers and its implications to relay of force.

The geometric shape of the filamentous, intrafascicular type of muscle fiber ending was reconstructed as a basis for understanding the pattern in relay of the fiber's force to the muscle tendon. Single motor units (MUs) identified physiologically as being fast and slow, respectively, were isolated in cat tibialis muscles and glycogen-depleted for recognition in cross sections of the muscle frozen at its Lo. Serial measurements of cross-sectional area (CSA) using an image processing system were made along 14 intrafascicular endings of MU fibers and an additional seven, non-depleted fibers identified histochemically as slow. Comparison of coefficients of variation for the linear relation of the CSAs and of the equivalent diameters with length along the taper indicated that in both fast and slow fibers the areas bore a closer relationship, that is, the taper had the equivalent of a parabolic, rather than a conical outline. The implications of these two conformations to relay of the fiber's contractile force to surrounding structures are displayed graphically.

Animals↗

Innervation patterns in the cat tibialis anterior six months after self-reinnervation.

The spatial distribution of fibers belonging to a single motor unit was analyzed in 10 motor units from the tibialis anterior of the cat 6 months after denervation and self-reinnervation of the anterior (superficial) compartment of the muscle. After self-reinnervation, the distribution patterns of the fibers in the fast motor units were significantly different than control, whereas the fiber distribution in the slow unit was similar to control. Reinnervated fast units had a significant increase in the number of adjacencies among motor unit fibers, and there were often distinct "clusters or groups" of fibers distributed within the motor unit territory. Clustering or grouping of fibers was evident within the motor unit, even though fiber type grouping was not evident within the muscle. The differences in distribution patterns between control and reinnervated units may be related to variations in the branching pattern of axons during reinnervation compared to the process that occurs during development.

Animals↗

Muscle fiber types and function.

In this review, we address current concepts and recent experimental results that relate to heterogeneity in the physiologic, biochemical, and morphologic properties of mammalian skeletal muscle fibers. Recent data reinforce some of these current concepts while questioning others. The biochemical bases of the concepts of fiber types continue to evolve, particularly in reference to the combinations of the myosin light and heavy chains that are expressed in most mammalian skeletal muscle fibers. Further, it is becoming increasingly clear that specific myosin isoforms relate to contractile function. What remains unclear, however, are the bases for a continuum in functional properties, eg, the maximum velocity of shortening, rather than distinct increments in these properties as might be predicted based on myosin isoforms alone. Clearly, there are factors other than myosin that play a role in defining the characteristics of a fiber, and some of these other factors are discussed. A second general issue addressed in this review is the source of the control of the heterogeneity among fibers of a skeletal muscle. Data are presented that demonstrate that this heterogeneity is not simply a function of the patterns of activation of motoneurons. It appears that the motoneuron can maintain practically all type-related features of fibers in the absence of neuromuscular activity. Although the motoneuron can influence muscle protein expression, it is equally clear that there are myogenic and hormonal factors that have significant regulatory roles. In effect, muscle fiber types reflect a complex interaction of multiple sources of control of protein expression, and the net effect of the control ultimately defines its functional properties.

Animals↗

Evidence of incomplete neural control of motor unit properties in cat tibialis anterior after self-reinnervation.

1. The mechanical, morphological and biochemical properties of single motor units from the anterior compartment of the tibialis anterior muscle in adult cats were studied six months after the nerve branches to that compartment were cut and resutured in close proximity to the muscle. 2. In these self-reinnervated muscles, the maximum tetanic tensions were lower in slow than fast units, a relationship similar to that observed among motor units from control adult muscles. The maximum tetanic tensions produced by the fast units were larger than those produced by the same motor unit types in control muscles. Direct counts of muscle fibres belonging to a motor unit showed that factors controlling the number of muscle fibres innervated by a motoneurone type persist during the reinnervation process in that fast motoneurones reinnervated more muscle fibres than slow motoneurones. Thus, the number of muscle fibres reinnervated by a motoneurone principally accounted for the difference in the maximum tension outputs among motor unit types, a relationship similar to that observed in control tibialis anterior muscles. 3. Monoclonal antibodies for specific myosin heavy chains were used to differentiate fibre types. By this criterion, motor units from control muscles were found to contain a homogeneous fibre type composition. In contrast, a heterogeneous, yet markedly biased, fibre type composition was observed in each unit analysed from self-reinnervated muscles. 4. Although not all of the muscle fibres of a motor unit developed the same type-associated parameters after reinnervation, the relationships among myosin heavy chain profile, succinate dehydrogenase activity and the fibre size were similar in fibres of control and self-reinnervated muscles. 5. The processes which dictate both motor unit size and the matching between motoneurone and muscle fibre type during the reinnervation process must be interdependent and result from a hierarchy of decisions which reflects their relative importance. The mechanisms responsible for these two processes may be a combination of: (1) selective innervation which may or may not incorporate a pruning process if multiple synaptic connections are initially formed and/or (2) conversion of enough fibres of a motor unit to form a predominant type.

Animals↗

Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight.

The objectives of the present study were to determine the size and enzyme properties of soleus fibers of rats subjected to a 4-day spaceflight (National Aeronautics and Space Administration, STS-41) and the effects of exogenous growth hormone (GH) on the atrophic response of the muscle. Four groups of rats were studied: 1) control (Con), 2) Con plus GH treated (Con + GH), 3) flight (Fl), and 4) F1 plus GH treated (Fl + GH). Cross-sectional area and the activities of succinate dehydrogenase and myofibrillar adenosinetriphosphatase (ATPase) were determined in fibers identified in frozen serial cross sections. Fibers were categorized immunohistochemically as slow, fast, or slow-fast on the basis of their reaction with slow and fast myosin heavy-chain (MHC) monoclonal antibodies. Fibers also were categorized as light or dark on the basis of their staining for ATPase at pH 8.6. After the 4-day flight, mean body weight was significantly decreased compared with control. The absolute and relative (muscle wt/body wt) soleus weights were significantly smaller in the Fl and Fl + GH rats compared with their respective ground-based controls. In both flight groups, the cross-sectional area of the light ATPase fibers was significantly smaller (approximately 30%) than control. Three of 11 flight rats had a higher proportion of fibers expressing both slow and fast MHCs than expected on the basis of the fiber type distribution in the 11 control rats. Mean fiber succinate dehydrogenase and ATPase activities were similar among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms.

A new technique for the sodium dodecyl sulfate-polyacrylamide gel electrophoretic separation of rat skeletal muscle myosin heavy-chain (MHC) isoforms is presented. This technique allows for the separation of the four identified MHC isoforms known to be present in adult rat skeletal muscle. These types of MHC are commonly called I, IIa, IIx or IId, and IIb. The procedure can be performed using minigel electrophoresis systems and does not involve preparation of gradient-separating gels or the use of special cooling devices. The procedure accommodates both silver and Coomasie Blue staining. Thus the procedure is simple to perform and highly repeatable, providing high-resolution separation of MHC protein isoforms. The percent composition of the four adult MHCs in rat soleus, medial gastrocnemius, diaphragm, and levator ani muscles by use of this procedure and Coomasie Blue staining is similar to that previously reported. This new technique provides a novel and easy-to-perform method for the separation of rat skeletal muscle MHC isoforms.

Animals↗

Adaptability of the oxidative capacity of motoneurons.

Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

Adaptation, Physiological↗

Physiological cross-sectional area of human leg muscles based on magnetic resonance imaging.

Magnetic resonance imaging techniques were used to determine the physiological cross-sectional areas (PCSAs) of the major muscles or muscle groups of the lower leg. For 12 healthy subjects, the boundaries of each muscle or muscle group were digitized from images taken at 1-cm intervals along the length of the leg. Muscle volumes were calculated from the summation of each anatomical CSA (ACSA) and the distance between each section. Muscle length was determined as the distance between the most proximal and distal images in which the muscle was visible. The PCSA of each muscle was calculated as muscle volume times the cosine of the angle of fiber pinnation divided by fiber length, where published fiber length:muscle length ratios were used to estimate fiber lengths. The mean volumes of the major plantarflexors were 489, 245, and 140 cm3 for the soleus and medial (MG) and lateral (LG) heads of the gastrocnemius. The mean PCSA of the soleus was 230 cm2, about three and eight times larger than the MG (68 cm2) and LG (28 cm2), respectively. These PCSA values were eight (soleus), four (MG), and three (LG) times larger than their respective maximum ACSA. The major dorsiflexor, the tibialis anterior (TA), had a muscle volume of 143 cm2, a PCSA of 19 cm2, and an ACSA of 9 cm2. With the exception of the soleus, the mean fiber length of all subjects was closely related to muscle volume across muscles. The soleus fibers were unusually short relative to the muscle volume, thus potentiating its force potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Enzyme and size profiles in chronically inactive cat soleus muscle fibers.

Spinal isolation (SI), i.e., the isolation of the lumbar spinal cord via a rostral and a caudal cord transection and bilateral dorsal rhizotomy, was used to determine the effects of chronic (6 months) inactivity on the size and metabolic properties of fibers in the cat soleus. Fibers were classified as dark or light, based on their staining reactions to myosin ATPase, alkaline preincubation, and immunohistochemically as expressing fast and/or slow myosin heavy chains (MHC). Succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) activities were assessed histochemically. Following SI, both the light and the dark ATPase fibers in the SI cats were significantly smaller than the light ATPase fibers in the controls. Normally 100% of the fibers were light ATPase and reacted exclusively with the slow antibody. After SI, approximately 45% of the fibers were dark ATPase fibers, many reacting with both fast and slow MHC antibodies. The total amount and concentration of GPD were higher in the light and dark ATPase fibers in SI compared with light ATPase fibers in controls. In contrast, although the total amount of SDH per fiber was decreased, reflecting the decrease in fiber size, the mean SDH concentration per fiber was unchanged following SI. These data indicate that there is a close coordination in the regulation of GPD activity and the type of myosin. SDH activity, on the other hand, appears to be resistant to decreased levels of activity and unloading, i.e., there seems to be a minimum level of oxidative potential in the soleus that is independent of activity level. Fiber sizes, however, are very sensitive to less-than-normal amounts of neuromuscular activity and/or loading.

Adenosine Triphosphatases↗

Variation and limitations in fiber enzymatic and size responses in hypertrophied muscle.

The present study was designed to determine whether the degree and kind of adaptation of a muscle fiber to a functional overload (FO) are determined by properties that are intrinsic to that fiber. The study also addresses the question of the capability of fibers to maintain a normal level of coordination of proteins per fiber as fiber volume changes dramatically. The plantaris muscle of six adult female cats was overloaded for 12 wk by bilateral synergist removal. Plantaris muscle fiber mean size doubled after FO, although some very small fibers that stained dark for adenosinetriphosphatase (ATPase) were observed in some of the FO muscles. There appeared to be no change in total succinate dehydrogenase activity per fiber. A reduction in succinate dehydrogenase activity per unit volume was observed in a substantial number of fibers, reflecting a disproportionate increase in fiber volume relative to mitochondrial volume. In contrast, total alpha-glycerophosphate dehydrogenase activity and actomyosin ATPase activity increased as fiber size increased, whereas there was no change in alpha-glycerophosphate dehydrogenase and ATPase activities per unit volume. Control and FO muscle fibers generally expressed either a fast or slow myosin heavy chain type, but in some cases FO muscle fibers expressed both fast and slow myosin heavy chains. The persistence of variability in fiber sizes and enzyme activities in fibers of overloaded muscles suggests a wide range in the adaptive potential of individual fibers to FO. These data indicate that a severalfold increase in cell size may occur without significant qualitative changes in the coordination of protein regulation associated with metabolic pathways and ATP utilization.

Adenosine Triphosphatases↗

Ventral horn cell responses to spaceflight and hindlimb suspension.

Spaceflight or hindlimb suspension results in a loss of mass and alterations of the metabolic and contractile protein profiles of skeletal muscles toward that resembling faster muscles. Given the influence of motoneurons on muscle properties, ventral horn cells of the lumbosacral enlargement of the spinal cord were studied to determine whether similar adaptations were present. Three groups of rats (5 per group) were studied: control, 14-day spaceflight, and 14-day hindlimb suspension. Spinal cords were quick-frozen, and the succinate dehydrogenase (SDH) activity and cross-sectional area of the soma of ventral horn cells were measured using a computer-enhanced image-processing system. Briefly, the optical density for SDH activity was determined after 8 min of incubation in a medium that gave a steady-state enzymatic reaction. Soma sizes were determined in cells with a visible nucleus. Although there were no significant differences among the three groups in mean cross-sectional area and SDH activity, the population distributions of both variables shifted significantly. In the flight rats, there was a shift toward smaller cells. Compared with control, the population distribution of SDH activities in the flight rats shifted toward higher activities, whereas the distribution shifted toward lower activities in the suspended rats. When considering the interactive effects within individual cells, there was a higher percentage of small cells with high SDH activities in the flight than in the control or suspended rats. These contrasting effects of spaceflight and hindlimb suspension suggest that the changes observed in ventral horn cells were due to factors other than simply the absence of weight support.

Animals↗

Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension.

Morphological and enzymatic responses in fibers expressing fast, slow, or both types of myosin heavy chain (MHC) were studied in rats after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Although the percentage of slow-twitch fibers was unchanged, a higher percentage of fibers that expressed both slow and fast MHC was observed in flight and suspended rats than in synchronous ground-based controls. The soleus was 25 and 34% smaller than control after 14 days of flight and suspension, with the reduction in fiber cross-sectional area (CSA) being greater in slow- than in fast-twitch fibers in both experimental groups. The activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) were not significantly affected by flight or suspension. The total SDH activity (i.e., SDH activity x CSA) decreased significantly in the slow-twitch fibers of the flight and the fast-twitch fibers of the suspended rats, in large part due to fiber atrophy. A shift in MHC expression in 14 and 9% of the fibers in flight and suspended rats occurred without a change in myosin adenosinetriphosphatase activity. The SDH and GPD activities of the fibers that expressed both slow and fast MHC were slightly higher than the slow-twitch fibers and slightly lower than the fast-twitch fibers. These data indicate that events were initiated within 14 days of spaceflight or suspension that began to reconfigure the protein profiles of 9-14% of the slow-twitch fibers from typical slow-twitch toward those of fast-twitch fibers, while all fibers were dramatically losing total protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

Adaptation of fibers in fast-twitch muscles of rats to spaceflight and hindlimb suspension.

The adaptation of single fibers in medial gastrocnemius (MG), a fast-twitch extensor, and tibialis anterior (TA), a fast-twitch flexor, was studied after 14 days of spaceflight (COSMOS 2044) or hindlimb suspension. Cross-sectional area (CSA) and succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar adenosinetriphosphatase (ATPase) activities were determined in fibers identified in frozen serial cross sections. Fibers were categorized as light, dark, or intermediate on the basis of myosin ATPase staining and alkaline preincubation and immunohistochemically as reacting with slow, fast, or both slow and fast myosin heavy chain monoclonal antibodies. Because there was a close relationship between these two means of categorizing fibers, all fibers were categorized on the basis of the immunohistochemical reaction. The percentage of slow- and fast-twitch fibers of the MG and TA were unchanged in either group. Mean fiber size of all fibers, irrespective of type, was unaffected in either muscle after flight or suspension. The fibers that expressed both fast and slow myosin heavy chains were smaller than control in the MG of both experimental groups. Compared with control, the SDH and total SDH activities in the MG were significantly less in suspended rats, with the fast-twitch fibers showing the largest difference. The ATPase activity in the MG was higher in flight than in control or suspended rats. There were no significant effects of flight on fibers of the TA. In contrast, the TA in suspended rats had higher GPD activities than either control or flight rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Spaceflight and growth effects on muscle fibers in the rhesus monkey.

Spaceflight causes considerable atrophy in hindlimb muscles of the rat. The purpose of this study was to investigate the effect of a 14-day spaceflight (COSMOS 2044) on selected morphological and metabolic properties of single muscle fibers in a nonhuman primate, Macaca mulatta. Biopsies were taken from the soleus (Sol), medial gastrocnemius (MG), and tibialis anterior (TA) muscles of two rhesus monkeys 107 days before flight and 24 h after return from flight. Muscle biopsies were taken from two independent sites in each muscle by use of a small (3-mm OD) Bergstrom biopsy needle. The biopsies weighed 8-14 mg and contained 100-200 fibers, of which an average of 40 fibers were acceptable for metabolic and size analyses. The 14-day spaceflight had little effect on fiber size in the Sol and MG muscles, whereas there appeared to be a slight decrease in size in the TA. In each of the flight animals, the mean fiber size in the postflight biopsies increased relative to preflight values. An increase in fiber size over the same period of time was also observed in four control monkeys that were the same age and approximately the same weight as the flight monkeys. The relative increase in size was related to the body weight of the monkey at the time of the pre- and postflight biopsies. The mean fiber succinate dehydrogenase activity appeared to decrease in the MG, whereas there was no apparent effect of spaceflight on the Sol and TA muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fibre size and type adaptations to spinal isolation and cyclical passive stretch in cat hindlimb.

Impulse activity is known to have a strong influence in determining the characteristics that distinguish skeletal muscle fibres into types. The control of muscle proteins by the neural systems that innervate the muscles, however, is not complete (Edgerton et al. 1985, 1990). The purpose of the present study, therefore, was to determine the effects of inactivity for 6 months on the size and fibre type composition of selected cat hindlimb muscles. Inactivity was produced by isolating the lumbar region of the spinal cord, i.e. transecting the cord at T12-T13 and again at L7-.S1 and then performing a bilateral dorsal rhizotomy between the transection sites (SI). In each SI cat, one hindlimb was passively manipulated for 30 min per day through a range of motion at the ankle mimicking a step cycle. SI resulted in an atrophic response in most muscles, with predominantly slow extensors showing the largest effect. In general, the predominant fibre type, which also had the largest mean size, in each muscle atrophied the most. The mean fibre size of all fibre types were similar after SI, suggesting that there may be a minimal size for inactive intact fibres. In comparison with control animals, all muscles in the SI cats had a higher proportion of fast fibres. Further, the relative contribution of the slow fibres to the total cross-sectional area of the muscle was decreased following SI. Some slow fibres in each muscle, however, were resistant to change. These data demonstrate the extent to which size and myosin type of mammalian muscle fibres are independent of activation characteristics.

Adaptation, Physiological↗