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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of central fatigue are largely unexplored, but the central fatigue hypothesis suggests that increased brain serotonin (5-HT) can cause a deterioration in sport and exercise performance. There is now convincing evidence that exercise-induced increases in the plasma free tryptophan (f-TRP)/branched-chain amino acids (BCCA) ratio are associated with increased brain 5-HT and the onset of fatigue during prolonged exercise. Furthermore, when drugs are administered to alter brain 5-HT, they have the predicted effects on exercise performance. The influence of nutritional manipulations of f-TRP/BCCA on performance is less well established. The effects of BCCA supplementation on exercise performance are mixed, and the published studies often suffer from methodological flaws. Alternatively, dramatic reductions in f-TRP/BCCA and enhanced performance accompany carbohydrate feedings during prolonged exercise. However, it is difficult to distinguish between the effects of carbohydrate feedings on mechanisms that reside in the brain versus the muscles themselves.
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PMID:Carbohydrates, branched-chain amino acids, and endurance: the central fatigue hypothesis. 755 Feb 56

Since the first comprehensive description of the symptoms of FMS by Yunus et al (1981), numerous investigations have confirmed that FMS is a clinical entity. However, the aetiology of the syndrome is still not fully elucidated. It seems, however, logical to place the origin of the disorder in the muscle. Muscle pain, especially at the muscle-tendon junctions, fatigue and stiffness are the first symptoms. A malfunction of energy metabolism has been detected in part of the muscle fibres. However, it has to be considered that the muscle is not an isolated entity. Its activity is controlled by segmentally arranged motor units of the ventral horn of the spinal cord in response to proprioceptive afferent signals arising in the muscle spindles or in other sensory elements including nociceptors. Together with supraspinal descending inputs, the spinal motor neurone pool is the common final pathway for segmental and suprasegmental inputs, making the motor system extremely powerful for adaptive adjustments but also vulnerable if deficits occur in either of these input levels. A second, recently discovered abnormality seen in FMS is a lowered serotonin level in peripheral and most likely also central structures. The underlying mechanism seems to be defective absorption of the precursor amino acid tryptophan from the gut. Serotonin is involved centrally in the regulation of the sleep pattern, and at the spinal level it acts as a 'gain setter' of motoneurone excitability and suppresses signal transmission of noxious stimuli in dorsal horn neurones. Either of these two disturbances, muscle energy depletion or serotonin deficiency, could by itself evoke many of the symptoms of FMS, and their combined appearance will perpetuate the disease. Depressed levels of somatomedin C, caused by a deficit of stage 4 sleep-dependent release of GH, might represent an additional factor in preventing proper development or repair of myoskeletal structures. Malabsorption of certain amino acids, possibly due to a genetic disorder of gut transport mechanisms, may constitute an additional deleterious factor. The abnormalities found in the HPA and HPT axis may be seen as an attempt of the organism to restore homeostasis. The stimulus eliciting this counter-regulatory reaction may be pain or other afferent signals which normally do not reach the central nervous system. It is doubtful whether the unspecific activation of the HPA axis in a non-inflammatory disease is beneficial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuromediator and hormonal perturbations in fibromyalgia syndrome: results of chronic stress? 785 Aug 79

We discussed mainly neurochemical etiology of affective disorders (A.D.). Neurochemically, decreased 5-HT uptake in the platelet, increased 5-HT2 receptor in the platelet and cortex of suicides, increased beta receptor in the brains of suicide, functional abnormality of alpha 2 receptor in clonidine, DMI test, GABAB receptor up-regulation after chronic administration of antidepressants and mood stabilizers, participation of neuropeptide Y, and abnormality of HPA axis were recognized. Moreover, we referred to the importance of psychosocial and genetic factors. As for the etiology of A.D., while predisposition and environment participate, the method of participation will be different in subtypes. Frailty to stress in a broad sense, however is commonly seen in A.D. Though psychosocial factors are important, the physical condition, which involves fatigue, cannot be ignored. And, it is the most important that the biological and genetical factors which cause A.D., in the face of stimuli, must first be elucidated.
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PMID:[Etiology of affective disorders]. 791 50

Several studies of the relationship of food intake to physical exercise strongly suggest that the two are closely linked. Serotonin transmission seems to be particularly important in the regulation of both appetite and central fatigue. Thus, the ingestion of branched-chain amino acids has been reported to decrease serotonin production and to improve physical performance. In the present study, the effects of three treatments (water, glucose, and branched-chain amino acids) were compared in 34 male Wistar rats. Maximal exercise duration, blood insulin, and glucose levels were measured. Results showed that following the ingestion of branched-chain amino acids, physical performance is lower and blood insulin level is higher than after glucose administration.
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PMID:Effects of administration of branched-chain amino acids vs. glucose during acute exercise in the rat. 819 Jul 72

The purpose of this experiment was to examine the effects of administration of serotonergic (5-HT) agonist and antagonist drugs on run-time to exhaustion (RUN-EXH) in male and female rats. RUN-EXH was reduced (p < 0.05) in a dose related manner by increasing dosages of quipazine dimaleate (QD: general 5-HT agonist) (0-5 mg.kg-1 i.p.) administered immediately prior to exercise (treadmill running at 20 m.min-1 and 5% grade). Conversely, RUN-EXH was increased (p < 0.05) by the greatest dosage of LY 53,857 (LY: 5-HT1C and 5-HT2 antagonist) (1.5 mg.kg-1 i.p.). Drug effects were similar in male and female rats. The negative effects of QD administration on RUN-EXH were not attenuated by administration of the peripherally restricted antagonist, xylamidine tosylate (up to 200 ug.kg-1 i.p.). The results of this investigation indicated that fatigue during prolonged exercise can be influenced by direct pharmacological administration of a serotonergic agonist and antagonist and that the mechanisms underlying these effects are likely to be central (brain) in nature.
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PMID:Serotonergic agonists and antagonists affect endurance performance in the rat. 782 75

Physical exercise influences the central dopaminergic, noradrenergic and serotonergic systems. A number of studies have examined brain noradrenaline (norepinephrine), serotonin (5-hydroxytryptamine; 5-HT) and dopamine with exercise. Although there are great discrepancies in experimental protocols, the results indicate that there is evidence in favour of changes in synthesis and metabolism of monoamines during exercise. There is a possibility that the interactions between brain neurotransmitters and their specific receptors could play a role in the onset of fatigue during prolonged exercise. The data on the effects of branched chain amino acid (BCAA) supplementation and 'central fatigue' seem to be conflicting, although recent studies suggest that BCAA supplementation has no influence on endurance performance. There are numerous levels at which central neurotransmitters can affect motor behaviour; from sensory perception, and sensory-motor integration, to motor effector mechanisms. However, the crucial point is whether or not the changes in neurotransmitter levels trigger or reflect changes in monoamine release. Until recently most studies were done on homogenised tissue, which gives no indication of the dynamic release of neurotransmitters in the extracellular space of living organisms. Recently, new techniques such as microdialysis are voltammetry were introduced to measure in vivo release of neurotransmitters. Microdialysis can collect virtually any substance from the brain of a freely moving animal with a limited amount of tissue trauma. This method allows measurement of local neurotransmitter release during on-going behavioural changes such as exercise. The results of the first studies using these methods indicate that the release of most neurotransmitters is influenced by exercise. Although the few studies that have been published to date show some discrepancies, we feel that these recently developed and more sophisticated in vivo methods will improve our insight into the relationship between the monoamine and other transmitters during exercise. Continued quantitative and qualitative research needs to be conducted so that a further understanding of the effects of exercise on brain neurotransmission can be gained.
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PMID:Exercise and brain neurotransmission. 857 Oct

To investigate the role of serotonin (5-HT) in the pathophysiology of panic disorder (PD) a challenge test with L-5-hydroxytryptophan (5-HTP) was conducted. Seven patients suffering from PD and seven healthy controls received an i.v. challenge with 10 mg, 20 mg and 40 mg 5-HTP and placebo in random order on four different occasions. Before, during and until 2 h after 5-HTP administration anxious and depressive symptomatology was assessed. In addition, plasma levels of 5-HTP, cortisol, and 5-HIAA were measured at several timepoints. During and after infusion of placebo or any of the different dosages of 5-HTP, none of the patients or controls experienced a panic attack or showed an increase in anxiety or depressive symptoms. There was a dose-related increase in side effects, like nausea, dizziness and fatigue. Only infusion with 40 mg 5-HTP led to an increase in plasma cortisol in both patients and controls. The observed increase in plasma cortisol level was higher for patients compared to controls only at 30 min after infusion. In conclusion, stimulation of the serotonergic neuronal system by three different dosages of 5-HTP did not induce panic or anxiety in PD patients and healthy controls. The 5-HT hypersensitivity hypothesis of PD could not be confirmed in the present study.
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PMID:Behavioral, neuroendocrine and biochemical effects of different doses of 5-HTP in panic disorder. 879 Oct 35

Aging is a physiological process that shares many behavioral, biochemical and neuroendocrine phenomena with the pathophysiological situation of unresolved stress, as well as with a pharmacologically induced syndrome resulting from chronic benzodiazepine (BZ) consumption. Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. Neuroendocrine findings include: central depletion of noradrenaline (NA), dopamine, adrenaline (AD), and serotonin (5-HT); reduction in the ratio of circulating NA/AD as well as platelet 5-HT and increase of AD, plasma free 5-HT and cortisol. These disturbances together with the increased platelet aggregability observed in the three groups are typical of unresolved-stress situations. Immunological findings include significant reduction of peripheral T lymphocytes (CD3, CD4, CD8) and the CD4/CD8 ratio, CD16 and gamma-delta cells. On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity. Alterations of several biological markers have also been found, specifically in the oral glucose tolerance test, the intramuscular clonidine test, and the supine/orthostasis/exercise test. From a clinical point of view, the three groups appear to be more susceptible to the appearance and progression of many acute and chronic diseases (infectious and malignant diseases). As a result, chronic consumption of BZs should be avoided in both the elderly and subjects in unresolved-stress situations.
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PMID:Benzodiazepines: tolerability in elderly patients. 884 97

Since the discovery of melatonin as the principal hormone of the pineal gland in 1963, scientists have come to recognize that melatonin is a "master hormone" involved in the control of circadian rhythms and other biological functions. Although little is known about the influence of the pineal gland on motor control, important clues may be obtained by considering the pattern of melatonin secretion during the sleep cycles and particularly during rapid eye movement (REM) sleep when melatonin plasma levels are at their lowest. Since REM sleep is characterized by the occurrence of profound atonia which results in an almost complete paralysis of striated muscles, it is suggested that there might be a causal relationship between inhibition of melatonin secretion during REM sleep and the development of REM sleep atonia. This relationship is supported by the findings that melatonin regulates the activity of brainstem serotonin (5-HT) neurons which characteristically cease to fire during REM sleep and which faciliate the development of REM sleep atonia. Moreover, as the muscular atonia of REM sleep is physiologically and pharmacologically indistinguishable from cataplexy, it is possible that the pineal gland also influences to the development of cataplexy. Cataplexy is an ancillary symptom of narcolepsy and also occurs in multiple sclerosis (MS). In fact, it is believed that several of the neurological symptoms experienced by patients with MS such as weakness in the legs, feeling of collapsing knees, paroxysmal sudden falling, weakness in the neck, extreme fatigue, intermittent paresthesias, slurring of speech and intermittent blurring of vision, which often are exacerbated by stress and other emotional influences, may reflect the manifestations of cataplexy. Thus, several of the clinical features of MS may reflect a dissociated state of wakefulness and sleep and may improve by the administration of anticataplectic drugs.
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PMID:The pineal gland, cataplexy, and multiple sclerosis. 886 24

The causes of fatigue during muscular exercise include factors that reside in the brain (central mechanisms) as well as the muscles themselves (peripheral mechanisms). Central fatigue is largely unexplored, but there is increasing evidence that increased brain serotonin (5-HT) can lead to central (mental) fatigue, thereby causing a deterioration in sport and exercise performance. Although there are also strong theoretical grounds for a beneficial role of nutrition in delaying central fatigue, the data are much more tenuous. Dietary supplementation with branched-chain amino acids (BCAA) in low doses produces small and probably inconsequential effects on peripheral markers of brain 5-HT synthesis (plasma free tryptophan/BCAA), whereas larger doses are likely to be unpalatable, reduce the absorption of water in the gut, and may increase potentially toxic ammonia concentrations in the plasma. Alternatively, carbohydrate supplementation results in large reductions in plasma free tryptophan/BCAA and exercise time to fatigue is significantly longer, but it is difficult to distinguish between the effects of carbohydrate feedings on central fatigue mechanisms and the well-established beneficial effects of carbohydrate supplements on the contracting muscle. These data support the exciting possibility that relationships exist among nutrition, brain neurochemistry and sport performance. However, while the evidence is intriguing and makes good intuitive sense, our knowledge in this area is rudimentary at best.
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PMID:Central and peripheral factors in fatigue. 889 20


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