Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise

The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN) neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting exercise. Dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were subsequently detected with high-performance liquid chromatography (HPLC). For immunohistochemistry study, the expression of DRD₂ and HT_2C receptors in the STN, before, immediately after and 90 min after exhaustion was detected through immunohistochemistry technique. Microdialysis study results showed that the extracellular DA and 5-HT neurotransmitters increased significantly throughout the procedure of exhausting exercise and the recovery period (P<0.05 or P<0.01). Immunohistochemistry study results showed that the expression levels of DRD₂ and HT_2C in the rat STN immediately after exhausting exercise and at the time point of 90 min after exhaustion were both higher than those of the rest condition, but the difference was not significant (P>0.05). Our results suggest that the increased extracellular DA and 5-HT in the STN might be one important factor leading to the enhanced STN neural activity and the development of fatigue during exhausting exercise. This study may essentially offer useful evidence for better understanding of the mechanism of the central type of exercise-induced fatigue.     

Recovery of the torque-velocity relationship after short exhausting cycling exercise

The effects of fatigue upon the torque-velocity (T-omega) relationship in cycling were studied in 11 subjects. Fatigue was induced by short exhausting exercise, on a cycle ergometer, consisting of 4 all-out sprints without recovery. The linear (T-omega) relationship was determined during each all-out sprint, before, during and after the exhausting exercise. The kinetics of the T-omega relationship had permitted the study of the recovery of optimal torque, optimal velocity and their corresponding maximal power outputs (Pmax), 30 s or 1 min after the short exhausting exercise. Fatigue induced a parallel shift to the left of the T-omega relationship which was partly reversed by a parallel shift to the right during recovery. After 30 s recovery optimal velocity, optimal torque and Pmax were slightly lower than the corresponding values before the exhausting exercise; after 1-min optimal velocity and optimal torque had recovered 99% and 97% of their initial values. These mechanical data suggested that the causes of exhaustion were processes that allowed fast recovery of both optimal velocity and optimal torque.     

A decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise in dogs.

The aim of the investigations carried out on dogs was to elucidate possible causes of the decreased hyperglycemic response to adrenaline after exhausting exercise. The k-values of i.v. glucose tolerance tests were calculated and the dose-response relationship to infused adrenaline was analyzed under control, resting conditions, and after exhausting exercise. K-values (KG-exc.) were significantly higher (p less than 0.01) after exercise than in control experiments, whereas hyperglycemic responses to the applied doses of adrenaline: 0.25, 0.5, 1.0, 2.0 and 3.0 mug-kg-1min-1 were considerably lower. In both situations a linear relationship was found between the hyperglycemic response and the dose of adrenaline, although the slope of the regression line, expressing this relationship, was significantly lower after exercise than that under control conditions. It is suggested that the decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise may be attributed to both the increased rate of glucose elimination from blood, and a decreased responsiveness of the liver to adrenaline.     

Combined effects of troglitazone and muscle contraction on insulin sensitization in Balb-c mouse muscle

Thiazolidinediones, represented by troglitazone, are insulin-sensitizing agents with proven efficacy for the treatment of type 2 diabetes. Exercise is also recommended for patients with type 2 diabetes because it both stimulates glucose uptake directly and it increases insulin sensitivity following exercise. The purpose of this study was to investigate the effects of troglitazone combined with exercise on 2-deoxyglucose (2DG) uptake in both the epitrochlearis and soleus muscle of Balb-c mice. Acute, 1-h treatment with troglitazone (10 or 20 microM), in the presence or absence of insulin, had no effect on 2DG uptake in either muscle. Chronic treatment with troglitazone by feeding enhanced the insulin sensitivity and responsiveness of 2DG uptake primarily in the epitrochlearis. Direct electrical stimulation of in situ muscle was used to model exercise while the contralateral muscle was used as the unexercised control. This model mimicked exercise in that glycogen was depleted, immediate 2DG uptake was enhanced, and there was a post-exercise increase in insulin sensitivity. Troglitazone feeding had no effect on 2DG uptake in the soleus when measured immediately after electrical stimultion. However, 2DG uptake in the unstimulated epitrochlearis from troglitazone-fed mice was elevated when measured immediately after removal such that no additional effects of the electrical stimulation were measured. We found that the insulin-sensitizing effect of troglitazone was not additive to the insulin-sensitizing effect of exercise, which suggests that troglitazone and exercise share similar pathways. A unique finding in this study was the differential response to troglitazone between the epitrochlearis (fast twitch) and the soleus (slow twitch) muscle types. Possible mechanisms are discussed.     

The treadmill exhausting test is not suitable for screening of growth hormone deficiency!

BACKGROUND/METHOD: We compared the growth hormone response to a modified exercise test--the treadmill exhausting test--to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. RESULTS: The mean +/- SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 +/- 1.3 in the pharmacological tests vs. 5.0 +/- 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean +/- SEM peak GH concentrations (ng/ml) of 5.5 +/- 0.5 in the pharmacological tests and 4.1 +/- 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. CONCLUSION: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.     

Role of xanthine oxidase in delayed lipid peroxidation in rat liver induced by acute exhausting exercise

The aim of this study was to examine whether xanthine oxidase (XOD)-derived hepatic oxidative damage occurs in the main not during but following strenuous exercise. The degree of damage to hepatic tissue catalyzed by XOD was investigated immediately and 3 h after a single bout of exhausting exercise, in allopurinol and saline injected female Wistar rats. Allopurinol treatment resulted in increased hypoxanthine and decreased uric acid contents in the liver compared with the saline treated group, immediately and 3 h after the exercise. Analysis immediately after the exercise showed no changes in hepatic hypoxanthine, uric acid, and thiobarbituric acid-reactive substance (TBARS) contents in the saline treated group, when compared with the resting controls. However, significant increases in uric acid contents in the saline treated livers were observed 3 h after the exercise, relative to the controls. Hepatic TBARS content in the saline treated group were markedly greater than those in both the control and allopurinol treated groups after 3 h of recovery following the exercise. It was concluded that a single bout of exhausting exercise may impose XOD-derived hepatic oxidative damage, primarily during the recovery phase after acute severe exercise.     

Anaerobic capacity determined by maximal accumulated O2 deficit

We present a method for quantifying the anaerobic capacity based on determination of the maximal accumulated O2 deficit. The accumulated O2 deficit was determined for 11 subjects during 5 exhausting bouts of treadmill running lasting from 15 s to greater than 4 min. The accumulated O2 deficit increased with the duration for exhausting bouts lasting up to 2 min, but a leveling off was found for bouts lasting 2 min or more. Between-subject variation in the maximal accumulated O2 deficit ranged from 52 to 90 ml/kg. During exhausting exercise while subjects inspired air with reduced O2 content (O2 fraction = 13.5%), the maximal O2 uptake was 22% lower, whereas the accumulated O2 deficit remained unchanged. The precision of the method is 3 ml/kg. The method is based on estimation of the O2 demand by extrapolating the linear relationship between treadmill speed and O2 uptake at submaximal intensities. The slopes, which reflect running economy, varied by 16% between subjects, and the relationships had to be determined individually. This can be done either by measuring the O2 uptake at a minimum of 10 different submaximal intensities or by two measurements close to the maximal O2 uptake and by making use of a common Y-intercept of 5 ml.kg-1.min-1. By using these individual relationships the maximal accumulated O2 deficit, which appears to be a direct quantitative expression of the anaerobic capacity, can be calculated after measuring the O2 uptake during one exhausting bout of exercise lasting 2-3 min.     

Aerobic metabolic scope and swimming performance in juvenile cod, Gadus morhua L.

Juvenile cod (Gadus morhua) were made to swim in a tunnel respirometer to determine the oxygen consumption during swimming at different speeds. Results were compared with measurements of standard and active metabolic rates in static respirometers before and after intense exercise. The oxygen consumption at maximum sustainable swimming speed was considerably lower than the peak oxygen consumption following exhausting exercise. It is suggested that these fish have a poorly developed system of aerobic (red) locomotor muscles which do not normally make a major demand upon oxygen consumption. Apparent specific dynamic action following feeding and repayment of oxygen debt following anaerobic exercise can each give rise to greater rates of oxygen consumption. Following exhausting exercise there is a delay of about 1 h before oxygen consumption reaches a peak level some 40% higher than the peak level observed during sustained swimming.     

The influence of exercise on muscle lysosomal enzymes

Representative lysosomal enzyme activities were measured in muscles taken 0 h and 24 h after an acute exercise run that was completed without any overt signs of fatigue. The animals had progressed 2 and 4 weeks into a standard exercise program which typically produces adaptive changes in the working muscles. There was an increase in acetylglucosaminidase activity (12%) in the fast-twitch red muscle section of all animals that participated in the training program. This small increase may be representative of a delayed response found after more exhausting exercise. The single exercise bout, however, did not cause any acute change in lysosomal activity nor alter the partition of lysosomal enzymes between the "free" and particulate fractions. Thus, altered lysosomal enzyme activity does not appear to be a contributing influence that challenges muscle fiber homeostasis during moderately intense running.     

Comparative MRI analysis of T2 changes associated with single and repeated bouts of downhill running leading to eccentric-induced muscle damage.

Although the exact mechanisms are still unclear, it is commonly acknowledged that acute eccentric exercise alters muscle performance, whereas the repetition of successive bouts leads to the disappearance of the deleterious signs. To clarify this issue, we measured blood creatine kinase and lactate dehydrogenase activities and proton transverse relaxation time (T2) in various leg muscles 72 h after single and repeated bouts of exhausting downhill running sessions (-15 degrees , 1.5 km/h) with either 4 or 7 days elapsed between bouts. After a single exercise bout, T2 and enzyme activities initially increased and recovered rapidly. When exercise bouts were repeated over a short time period (4 days), initial changes did not recover and endurance time throughout additional exercise sessions was significantly reduced. On the contrary, with a longer resting time between exercises (7 days), the endurance time of additional running sessions was significantly longer and muscle changes (T2 increase, muscle edema, and enzyme activity changes) slowly and completely reversed. Significant correlations were found between T2 changes and enzyme activities. T2 changes in the soleus and gastrocnemius muscle heads were differently affected by lengthening contractions, suggesting a muscle specificity and indicating that muscle alterations might be linked to different anatomical properties, such as fiber pennation angles, typology, and/or the exhausting nature of the downhill running sessions. We documented a "less muscle injury" effect due to the repetition of exercise bouts at a low frequency (i.e., 1 session per week) in accordance with the delayed muscle inflammation. This effect was not observed when the between-exercise resting time was shorter.     

大鼠力竭运动中丘脑底核和皮层神经元电活动的变化

目的：探讨力竭过程中丘脑底核（SIN）对皮层兴奋性的调控作用。方法：采用皮层脑电（ECoG）及局部场电（LFPs）同步记录技术,对一次性力竭运动过程中大鼠SIN、皮层神经元电活动变化规律进行同步、动态观察。结果：运动开始阶段大鼠能够自主跟随跑台进行运动,运动持续约45min时（45±11．5min）,自我驱动下的运动能力明显降低;此时STN兴奋性显著增加（P〈0．01）,皮层兴奋性显著下降（P〈0．01）。如果给予大鼠一定的外部刺激后仍可继续运动一段时间直至力竭;力竭即刻皮层兴奋性降到最低值（P〈0．01）,而SIN兴奋性变化不显著（P〉0．05）。结论：大鼠在力竭运动过程中,皮层运动区神经元电活动随着运动疲劳的发生呈现广泛的抑制现象,而SIN神经元电活动在疲劳初期则明显增强,SIN通过负诱导作用参与了运动性中枢疲劳的调控,且STN神经元兴奋性增强可能是皮层实现保护性抑制机制的重要途径之一。     

Intracellular monocyte and serum cytokine expression is modulated by exhausting exercise and cold exposure

This study tested the hypothesis that exercise elicits monocytic cytokine expression and that prolonged cold exposure modulates such responses. Nine men (age, 24.6 +/- 3.8 y; VO(2 peak), 56.8 +/- 5.6 ml. kg(-1). min(-1)) completed 7 days of exhausting exercise (aerobic, anaerobic, resistive) and underwent three cold, wet exposures (CW). CW trials comprised 相似文献   

Analysis of trace amino acid neurotransmitters in hypothalamus of rats after exhausting exercise using microdialysis

A simple but effective coupling of microdialysis and capillary electrophoresis with laser induced fluorescence detection technique was applied to analysis of amino acid neurotransmitters in the hypothalamus of rats after acute exhausting exercise. The separation of amino acids was achieved using an uncoated fused-silica capillary (57 cm×75 μm I.D.) with a buffer of 10 mM disodium tetraborate at pH 10 and an applied voltage of 12.5 kV. The detection limit was 10⁻¹⁰ M for each amino acid. It is sufficiently sensitive and rapid for the determination of amino acids in a 5-μl Microdialysate. In comparison to pre-exercise, a significant increase in the levels of six hypothalamic amino acids (arginine, glycine, lysine, glutamic acid, alanine, γ-amino-n-butyric acid) was found after exercise. These results demonstrate that the increase of metabolic amino acids in the hypothalamus of rats can be induced by exhausting exercise and suggests that amino acid neurotransmitters may play functional roles in the central effects of exercise.     

Effect of training on hormonal responses to exercise in competitive swimmers.

The effects of 9 weeks of training on responses of plasma hormones to swimming were studied in eight competitive swimmers who had not trained for several months. Two types of swimming tests were used: (1) 200 yd, a high intensity, exhausting type of exercise in which maximal effort was required both before and after training, and (2) 1000 yd, a pace type of exercise in which subjects swam as fast as possible prior to training and at the same rate after training. Plasma levels of glucagon increased and of insulin decreased during 1000 yd of swimming, but were not altered by 200 yd of swimming. No training effects were apparent in responses of plasma insulin and glucagon to these shortterm, high intensity exercise tests. During the 1000 yd swim, plasma adrenaline was 0.8 ng/ml before vs. 0.1 ng/ml after training. Plasma noradrenaline response decreased from 3.4 to 1.2 ng/ml as a result of training. In the 200 yd swim, adrenaline, but not noradrenaline, was lower after training.     

EMG median power frequency in an exhausting exercise

EMG median power frequency of the calf muscles was investigated during an exhausting treadmill exercise. This exercise was an uphill run, the average endurance time was 1.5 min. Median power frequency of the calf muscles declined by more than 10% during this exercise. In addition EMG median power frequency of isometric contractions of the same muscles was measured before and in one minute intervals for 10 min after this run. Immediately after the run isometric median power frequency had declined by less than 5% for the soleus muscle, more than 10% for the gastrocnemius medialis and gastrocnemius lateralis muscles. In the 10 min following exercise the isometric median power frequency increased to pre-execise levels. Maybe the median power frequency shift to lower frequencies during dynamic exercise can be interpreted as a sign of local muscle fatigue.     

Effects of a rapid change in muscle glycogen availability on metabolic and hormonal responses during exercise

To evaluate the metabolic and hormonal adaptations following a rapid change in muscle glycogen availability, 14 subjects had their muscle glycogen content increased in one leg (IG) and decreased in the other (DG). In group A (n = 7), subjects exercised on a bicycle ergometer at 70% maximal oxygen uptake for 20 min using the DG leg. Without resting these same subjects exercised another 20 min using the IG leg. Subjects in group B (n = 7) followed the same single-leg exercise protocol but in the reverse order. In order to get some information on the time sequence of these possible adaptations, blood samples were collected at rest and at the beginning and the end of each exercise period (min 5, 20, 25, and 40). Results indicated that 5 min after the switch from the DG leg to the IG leg, transient increases in plasma free fatty acids (1.20 to 1.39 meq X 1(-1)) and serum insulin (10.1 to 12 mu X 1(-1)) concentrations occurred. Between minute 25 and 40 of exercise, the DG to IG switch was accompanied by a decrease in free fatty acids and glycerol concentrations as well as an increase in lactate levels. An opposite response was observed in the IG to DG condition during the same time span. Plasma norepinephrine, epinephrine, glucagon, and serum cortisol concentrations were not significantly affected by the leg change. These results suggest a rapid preferential use of muscle glycogen when available and a time lag in the response of the extramuscular substrate mobilization factors.     

Exercise and glycogen depletion: effects on ability to activate muscle phosphorylase

Phosphorylase activation reverses during prolonged contractile activity. Our first experiment was designed to determine whether this loss of ability to activate phosphorylase by stimulation of muscle contraction persists following exercise. Phosphorylase activation by stimulation of muscle contraction was markedly inhibited in rats 25 min after exhausting exercise. To evaluate the role of glycogen depletion, we accelerated glycogen utilization by nicotinic acid administration. A large difference in muscle glycogen depletion during exercise of the same duration did not influence the blunting of phosphorylase activation. Phosphorylase activation by stimulation of contraction was more severely inhibited following prolonged exercise than after a shorter bout of exercise under conditions that resulted in the same degree of glycogen depletion. A large difference in muscle glycogen repletion during 90 min of recovery was not associated with a significant difference in the ability of muscle stimulation to activate phosphorylase, which was still significantly blunted. Phosphorylase activation by epinephrine was also markedly inhibited in muscle 25 min after strenuous exercise but had recovered completely in glycogen-repleted muscle 90 min after exercise. These results provide evidence that an effect of exercise other than glycogen depletion is involved in causing the inhibition of phosphorylase activation; however, they do not rule out the possibility that glycogen depletion also plays a role in this process.     

Ultrastructural and gene-expression changes in the calcium regulation system of rat skeletal muscles under exhausting exercise

The expression of genes responsible for the synthesis of essential proteins regulating the calcium-ion balance and ultrastructural characteristics of fast-twitch (m. extensor digitorum longus, EDL) and slow-twitch (m. soleus, SOL) skeletal muscles under prolonged exercise were studied in an experimental model of forced-swimming rats. A day after the end of the exercise, no significant changes in any of the five investigated genes were revealed in the SOL. A few triad elements (T-tubules and cisternae of sarcoplasmic reticulum) were revealed. A small number of excitation-contraction coupling (ECC) structures in the control and a slight increase in their amount after exercises were noticed. Polymorphism and mitochondrial defects within SOL muscles indicate the importance of these structures in the regulation of calcium balance. In EDL muscles, adaptation mechanisms are aimed mainly at pumping Ca²⁺ ions to the sarcoplasmic reticulum, where the main calcium buffer is calsequestrin. Expression of SERCA1 gene increased by an order of magnitude, and that of CASQ1 increased by three times. Electron microscopy showed a major role of triads in the maintenance of calcium homeostasis in the EDL muscles, as well as a greater destruction of these muscles compared to SOL after exhausting exercise. The high level of triads and a possible activation of the CICR (calcium-induced calcium release) mechanism in fast-twitch muscles can cause damage to them during exhausting exercise. Adaptation of SOL muscles is associated with structural rearrangements of the mitochondrial apparatus, while adaptation of the EDL muscles is caused by calcium removal from the sarcoplasm with Ca-ATPase and its retention in the sarcoplasmic reticulum by calsequestrin.     

Effect of antioxidant vitamin treatment on the time course of hematological and hemorheological alterations after an exhausting exercise episode in human subjects.

This study examined the effects of a 2-mo antioxidant vitamin treatment on acute hematological and hemorheological alterations induced by exhausting exercise; both sedentary and trained individuals were employed. Eighteen young male, human subjects (9 sedentary, 9 trained by regular exercise) participated in the study and performed an initial maximal aerobic cycle ergometer exercise with frequent blood sampling over a 24-h period and analysis of hematological and hemorheological parameters. All subjects were treated with an antioxidant vitamin A, C, and E regimen, supplemented orally for 2 mo, and then subjected to a second exercise test and blood sampling at the end of this period. In the sedentary group during the first testing period (before vitamin treatment), white blood cell counts and granulocyte percentages were increased at 2 h after the exercise test and remained elevated for 4-12 h. Red blood cell (RBC) deformability and aggregation were also altered by exercise in the sedentary group before vitamin treatment. However, none of these parameters in the sedentary group were altered by exercise after the 2-mo period of antioxidant vitamin treatment. With the exception of a transient rise in granulocyte percentage, these parameters were also not affected in the trained subjects before the vitamin treatment. Significant increases of RBC lipid peroxidation observed 12 h after the exercise test in both sedentary and trained subjects were also totally prevented by vitamin treatment. Our results indicate that antioxidant vitamin treatment is effective in preventing the inflammation-like response and coincident adverse hemorheological changes after an episode of exhausting exercise, and suggest that such changes may be related to exercise-induced death events.     

Leptin, gastrointestinal and stress hormones in response to exercise in fasted or fed subjects and before or after blood donation.

Leptin, an ob gene product of adipocytes, plays a key role in the control of food intake and energy expenditure but little is known about leptin response to strenuous exercise in fasted and fed subjects or before and after blood donation. This study was designed to determine the immediate effects of strenuous exercise in healthy volunteers under fasting or fed conditions and before and one day after blood donation (450 ml) on plasma levels of leptin and gut hormones [gastrin, cholecystokinin (CCK), pancreatic polypeptide (PP) and insulin], as well as on "stress" hormones (cortisol, catecholamines and growth hormone. Two groups (A and B) of healthy non-smoking male volunteers were studied. All subjects performed incremental exercise tests until exhaustion (up to maximal oxygen uptake--VO2max), followed by 2 h of rest session. Group A perfomed the tests on a treadmill, while group B on a cycloergometer. In group A, one exercise was performed under fasting conditions and the second following ingestion of a standard liquid meal. In group B, one exercise test was performed as a control test and the second 24 h after blood donation (450 ml). Blood samples were withdrawn 5 min before the start of the test, at the VO2max, and 2 h after finishing the exercise. No significant change in plasma teptin were observed both immediately and 2 h after the exercise in fasted subjects, but after the meal the plasma leptin at VO2max and 2 h after the test was significantly higher, while after blood donation was significantly reduced. The postprandial rise in plasma leptin was accompanied by a marked increment in gut hormones; gastrin, CCK and PP and stress hormones such as norepinephrine, cortisol and GH. These hormonal changes could contribute to the postprandial rise in plasma leptin concentrations, while the fall of leptin after blood donation could be attributed to the inadequate response of stress hormones and autonomic nervous system to exhausting exercise. We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation and 3) following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin, cortisol and GH concentrations, possibly due to the impairment in the autonomic nervous control of these hormones.