Glucocorticoid receptor activation during exercise in muscle

This investigation was undertaken to evaluate whether endurance running of the type known to retard the muscle atrophy associated with glucocorticoid excess inhibits activation of glucocorticoid-receptor complexes to a DNA binding state. Female adrenalectomized rats received an injection (50 microCi/100 g body wt ip) of [3H]triamcinolone acetonide and remained sedentary or were immediately exercised by endurance running at 23 m/min for up to 90 min. Receptor activation, as quantified by binding to DNA-cellulose, steadily increased from 10-20% of the receptors capable of binding DNA in uninjected controls to 25-45% by 5 min and to 53-80% by 90 min after receiving the hormone in all muscles studied (fast-twitch red vastus lateralis, fast-twitch white vastus lateralis, slow-twitch soleus, mixed gastrocnemius, and heart). Exercise did not influence the time-course changes in percent activation. When activation was determined from changes in the conformational state of the receptor as measured by diethylaminoethyl-cellulose anion exchange chromatography, there was a similar time-dependent formation of activated receptor forms in all muscle types. However, exercise did not inhibit or delay the appearance of the activated receptor from the unactivated state. These results indicate that glucocorticoid receptor activation occurs at a rate that is independent of both fiber type and delivery of steroid to working muscles during exercise. If exercise alters receptor activation, a longer time period, beyond 90 min of running, or even additional training may be needed for inhibition to be expressed.     

Central and peripheral hemodynamics during maximal leg extension exercise

The purpose of this study was to examine the central and peripheral hemodynamic adaptations to maximal leg extension exercise. Seventeen men (X = 25 years, 84 kg) performed leg extension exercise (Universal equipment) for 12 repetitions (90s) to fatigue. Each repetition consisted of a 3s lifting motion, 1s pause, and 3s lowering motion. Impedance cardiography was used to measure stroke volume (SV), cardiac output (Q), systolic time intervals, and impedance contractility indices on a beat-by-beat basis. There were significant increases in systolic, diastolic, mean arterial pressure, total peripheral resistance, and HR during exercise. The mean Q remained similar throughout the protocol. SV decreased even though indices of myocardial performance indicated an enhancement of contractility. The magnitude of Q and SV were dependent upon the phase of leg extension. SV and Q during the lifting portions of the exercise were smaller than the lowering portions. The differences in SV and Q during the concentric and eccentric phases of the exercise most likely reflect the large static forces in exercising muscle which impeded venous return and increased afterload.     

Endurance exercise training attenuates leucine oxidation and BCOAD activation during exercise in humans

We studied the effects of a 38-day endurance exercise training program on leucine turnover and substrate metabolism during a 90-min exercise bout at 60% peak O(2) consumption (VO(2 peak)) in 6 males and 6 females. Subjects were studied at both the same absolute (ABS) and relative (REL) exercise intensities posttraining. Training resulted in a significant increase in whole body VO(2 peak) and skeletal muscle citrate synthase (CS; P < 0.001), complex I-III (P < 0.05), and total branched-chain 2-oxoacid dehydrogenase (BCOAD; P < 0.001) activities. Leucine oxidation increased during exercise for the pretraining trial (PRE, P < 0.001); however, there was no increase for either the ABS or REL posttraining trial. Leucine oxidation was significantly lower for females at all time points during rest and exercise (P < 0.01). The percentage of BCOAD in the activated state was significantly increased after exercise for both the PRE and REL exercise trials, with the increase in PRE being greater (P < 0.001) compared with REL (P < 0.05). Females oxidized proportionately more lipid and less carbohydrate during exercise compared with males. In conclusion, we found that 38 days of endurance exercise training significantly attenuated both leucine oxidation and BCOAD activation during 90 min of endurance exercise at 60% VO(2 peak) for both ABS and REL exercise intensities. Furthermore, females oxidize proportionately more lipid and less carbohydrate compared with males during endurance exercise.     

Effect of pre-exhaustion exercise on lower-extremity muscle activation during a leg press exercise

The purpose of this study was to investigate the effect of pre-exhaustion exercise on lower-extremity muscle activation during a leg press exercise. Pre-exhaustion exercise, a technique frequently used by weight trainers, involves combining a single-joint exercise immediately followed by a related multijoint exercise (e.g., a knee extension exercise followed by a leg press exercise). Seventeen healthy male subjects performed 1 set of a leg press exercise with and without pre-exhaustion exercise, which consisted of 1 set of a knee extension exercise. Both exercises were performed at a load of 10 repetitions maximum (10 RM). Electromyography (EMG) was recorded from the rectus femoris, vastus lateralis, and gluteus maximus muscles simultaneously during the leg press exercise. The number of repetitions of the leg press exercise performed by subjects with and without pre-exhaustion exercise was also documented. The activation of the rectus femoris and the vastus lateralis muscles during the leg press exercise was significantly less when subjects were pre-exhausted (p < 0.05). No significant EMG change was observed for the gluteus maximus muscle. When in a pre-exhausted state, subjects performed significantly (p < 0.001) less repetitions of the leg press exercise. Our findings do not support the popular belief of weight trainers that performing pre-exhaustion exercise is more effective in order to enhance muscle activity compared with regular weight training. Conversely, pre-exhaustion exercise may have disadvantageous effects on performance, such as decreased muscle activity and reduction in strength, during multijoint exercise.     

Neuromuscular activation of vastus intermedius muscle during fatiguing exercise

The purpose of this study was to investigate neuromuscular activation of the vastus intermedius (VI) muscle during fatiguing contraction. Seven healthy men performed sustained isometric knee extension exercise at 50% of maximal voluntary contraction until exhaustion. During the fatiguing task, surface electromyograms (EMGs) were recorded from four muscle components of the quadriceps femoris muscle group: VI; vastus lateralis (VL); vastus medialis (VM); and rectus femoris (RF) muscles. For the VI muscle, our recently developed technique was used. Root mean square (RMS) and median frequency (MF) of the surface EMG signal were calculated and these variables were then normalized by the value at the beginning of the task. Normalized RMS of the VI muscle resembled those of the other three muscles at all given times. At 95% of exhaustion time, normalized MF of the VI muscle was significantly higher than that of the VL muscle (p < 0.05). These results suggested that neuromuscular activation is not consistent between the VI and VL muscles at the exhaustion for isometric submaximal contraction and this could reflect the dissimilar intramuscular metabolism between these muscles.     

Central nervous system and computation

Computational systems are useful in neuroscience in many ways. For instance, they may be used to construct maps of brain structure and activation, or to describe brain processes mathematically. Furthermore, they inspired a powerful theory of brain function, in which the brain is viewed as a system characterized by intrinsic computational activities or as a "computational information processor. "Although many neuroscientists believe that neural systems really perform computations, some are more cautious about computationalism or reject it. Thus, does the brain really compute? Answering this question requires getting clear on a definition of computation that is able to draw a line between physical systems that compute and systems that do not, so that we can discern on which side of the line the brain (or parts of it) could fall. In order to shed some light on the role of computational processes in brain function, available neurobiological data will be summarized from the standpoint of a recently proposed taxonomy of notions of computation, with the aim of identifying which brain processes can be considered computational. The emerging picture shows the brain as a very peculiar system, in which genuine computational features act in concert with noncomputational dynamical processes, leading to continuous self-organization and remodeling under the action of external stimuli from the environment and from the rest of the organism.     

Central nervous system drug design

A model which suggests that there is a common structural basis for the action of many different classes of CNS drugs is described. It is shown that this general model is consistent with specific models for opioid analgesic and antidepressant activity. The significance of these models is not only that they define specific spatial relationships between the structural requirements in different CNS drug classes, but also that they allow the formulation of three very simple drug design techniques which will be referred to as pruning, splicing and grafting. When combined with available structure-activity information, these techniques may provide a rational approach to the design of drugs with specified CNS activity.     

Influence of muscle mass on sympathetic neural activation during isometric exercise

The primary purpose of this study was to determine whether the sympathetic neural activation induced by isometric exercise is influenced by the size of the contracting muscle mass. To address this, in nine healthy subjects (aged 19-27 yr) we measured heart rate, systolic arterial blood pressure, and muscle sympathetic nerve activity in the leg (MSNA; peroneal nerve) before (control) and during 2.5 min of isometric handgrip exercise (30% of maximal voluntary force). Exercise was performed with the right and left arms separately and with both arms simultaneously (random order). During exercise, heart rate, systolic pressure, and MSNA increased above control under all conditions (P less than 0.05). For each variable, the magnitudes of the increases from control to the end of exercise were significantly greater when exercise was performed with two arms compared with either arm alone (P less than 0.05). In general, the increases in heart rate, systolic pressure, and MSNA elicited during two-arm exercise were significantly less than the simple sums of the responses evoked during exercise of each arm separately. These findings indicate that the magnitude of the sympathetic neural activation evoked during isometric exercise in humans is determined in part by the size of the active muscle mass. In addition, our results suggest that the sympathetic cardiovascular adjustments elicited during exercise of separate limbs are not simply additive but instead exhibit an inhibitory interaction (i.e., neural occlusion).     

Effects of fasting and training on pyruvate dehydrogenase activation during exercise

1. The effect of exercise (2 hr treadmill running at 28 m/min) on PDHa (the activity of the active form of pyruvate dehydrogenase) in untrained rats, trained rats (2 hr/d at 25 m/min for 4 wk), and in 24 hr fasted rats was determined. 2. Exercise increased PDHa activity approximately 2 fold in fed-untrained rats. 3. Fasting decreased PDHa activity in sedentary rats to approximately half the activity in fed rats. 4. The increase in PDHa activity during exercise was less in fasted than fed rats. 5. Training did not change the total activity of PDH (phosphorylated plus nonphosphorylated forms) but the percent of PDH in the active form was increased in muscle of trained-rested rats. 6. PDHa activity was unchanged by acute exercise (2.5 hr at 40 m/min) in the trained rats.     

Relationship between skin temperature and muscle activation during incremental cycle exercise

While different studies showed that better fitness level adds to the efficiency of the thermoregulatory system, the relationship between muscular effort and skin temperature is still unknown. Therefore, the present study assessed the relationship between neuromuscular activation and skin temperature during cycle exercise. Ten physically active participants performed an incremental workload cycling test to exhaustion while neuromuscular activations were recorded (via surface electromyography – EMG) from rectus femoris, vastus lateralis, biceps femoris and gastrocnemius medialis. Thermographic images were recorded before, immediately after and 10 min after finishing the cycling test, at four body regions of interest corresponding to the muscles where neuromuscular activations were monitored. Frequency band analysis was conducted to assess spectral properties of EMG signals in order to infer on priority in recruitment of motor units. Significant inverse relationship between changes in skin temperature and changes in overall neuromuscular activation for vastus lateralis was observed (r<−0.5 and p<0.04). Significant positive relationship was observed between skin temperature and low frequency components of neuromuscular activation from vastus lateralis (r>0.7 and p<0.01). Participants with larger overall activation and reduced low frequency component for vastus lateralis activation presented a better adaptive response of their thermoregulatory system by showing fewer changes in skin temperature after incremental cycling test.     

Sympathetic activation is associated with increases in EMG during fatiguing exercise

The purpose of this study was to test the hypothesis that efferent sympathetic neural discharge is coupled with the development of muscle fatigue during voluntary exercise in humans. In 12 healthy subjects (aged 20-34 yr) we measured heart rate (HR), arterial blood pressure (AP), and noncontracting, skeletal muscle sympathetic nerve activity (MSNA) in the leg (peroneal nerve) before (control) and during each of three trials of submaximal (30% of maximum) isometric handgrip exercise performed to exhaustion. In six of the subjects of eletromyographic (EMG) activity of the exercising forearm was also measured. HR and AP increased significantly (P less than 0.05) in the 1st min of exercise in all trials. In contrast, neither MSNA nor EMG activity increased significantly above control during the 1st min of exercise, but both parameters subsequently increased in a progressive and parallel manner (P less than 0.05). The overall correlation coefficient between MSNA and EMG activity (144 observations) was 0.85 (P less than 0.001). With successive trials the magnitudes of the increases in HR, AP, MSNA, and EMG activity were greater at any absolute point in time during exercise. These results indicate that sympathetic activation to noncontracting skeletal muscle is directly related to the development of muscle fatigue (as assessed by the change in EMG) during prolonged isometric exercise in humans. Furthermore, our findings demonstrate that previous fatiguing contractions alter the time course of the sympathetic neural adjustments to exercise.     

Voluntary activation of human quadriceps during and after isokinetic exercise.

The extent of voluntary activation in fresh and fatigued quadriceps muscles was investigated during isometric and isokinetic voluntary contractions at 20 and 150 degrees/s in 23 normal human subjects. The muscles were fatigued by a total of 4 min of maximal knee extension at an angular velocity of 85 degrees/s. Voluntary activation was determined by the superimposition of tetanic electrical stimulation at 100 Hz for 250 ms, initiated at a constant knee angle. The relationship between voluntary and stimulated force was similar to that found with the established twitch superimposition technique used on isometric contractions. In fresh muscle all the subjects showed full voluntary activation during isometric contractions. Some activation failure was seen in five subjects at 20 degrees/s [2.0 +/- 0.9 degrees (SE)] and in two subjects at 150 degrees/s (0.7 +/- 0.5). After fatigue all subjects showed some activation failure at 0 and 20 degrees/s (36.4 +/- 3.1 and 28.8 +/- 4.1 degrees, respectively), but only two showed any at 150 degrees/s (1.4 +/- 5.7). We conclude that brief high-intensity dynamic exercise can cause a considerable failure of voluntary activation. This failure was most marked during isometric and the lower-velocity isokinetic contractions. Thus a failure of voluntary activation may have greater functional significance than previous studies of isometric contractions have indicated.     

Altered mechanisms of sympathetic activation during rhythmic forearm exercise in heart failure

In congestive heart failure (CHF), themechanisms of exercise-induced sympathoexcitation are poorly defined.We compared the responses of sympathetic nerve activity directed tomuscle (MSNA) and to skin (SSNA, peroneal microneurography) duringrhythmic handgrip (RHG) at 25% of maximal voluntary contraction andduring posthandgrip circulatory arrest (PHG-CA) in CHF patients with those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similarin both groups (CHF patients, n = 12;controls, n = 10). However, duringPHG-CA, in the controls MSNA returned to baseline, whereas it remainedelevated in CHF patients (P < 0.05).Similarly, at end exercise, the increase in SSNA was comparable in bothgroups (CHF patients, n = 11;controls, n = 12), whereas SSNAremained elevated during PHG-CA in CHF patients but not in the controls (P < 0.05). In a separate controlgroup (n = 6), even high-intensity static handgrip was not accompanied by sustained elevation of SSNAduring PHG-CA. ³¹P-nuclear magneticresonance spectroscopy during RHG demonstrated significant muscleacidosis and accumulation of inorganic phosphate in CHF patients(n = 7) but not in controls(n = 9). We conclude that in CHFpatients rhythmic forearm exercise leads to premature fatigue andaccumulation of muscle metabolites. The prominent PHG-CA response ofMSNA and SSNA in CHF patients suggests activation of the musclemetaboreflex. Because, in contrast to controls, in CHF patients bothMSNA and SSNA appear to be under muscle metaboreflex control, themechanisms and distribution of sympathetic outflow during exerciseappear to be different from normal.