Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

Jammes, Yves; Adjriou, Nabil; Kipson, Nathalie; Criado, C. Fernandez; Charpin, C; Stavris, C.; Guieu, Régis; Fenouillet, Emmanuel; Rétornaz, F.

doi:10.1186/s12967-020-02341-9

Cited by 11 publications

(13 citation statements)

References 30 publications

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“…3 ). There is also evidence for an inhibition of the Na + /K + -ATPase by reactive oxygen species (ROS) in ME/CFS patients that may stem from inflammatory processes or mitochondrial dysfunction [ 43 ]. During prolonged exercise for example even in the healthy situation oxidative stress may reduce Na + /K + -ATPase activity via glutathionylation [ 39 ].…”

Section: Disturbances Of Ions In Skeletal Muscles In Me/cfs As the Mamentioning

confidence: 99%

“…2 ). There is evidence for a reduced potassium efflux in exercising muscle in ME/CFS patients which can only be explained by the development of intracellular hypokalemia as a consequence of a diminished activity of the Na + /K + -ATPase [ 43 ]. These authors incriminate ROS to inhibit the Na + /K + -ATPase [ 39 ].…”

Section: Disturbances Of Ions In Skeletal Muscles In Me/cfs As the Mamentioning

confidence: 99%

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Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Wirth¹,

Scheibenbogen

2021

J Transl Med

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Chronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis). An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis. The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia–reperfusion paradigm. The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.

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Section: Disturbances Of Ions In Skeletal Muscles In Me/cfs As the Mamentioning

confidence: 99%

Section: Disturbances Of Ions In Skeletal Muscles In Me/cfs As the Mamentioning

confidence: 99%

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Wirth¹,

Scheibenbogen

2021

J Transl Med

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“…The protocol used to investigate the exercise potential in patients with ME/CFS has been published previously [14][15][16]. The exercise trial was performed on an electrically braked cycle ergometer (eBike General Electric, USA) driven by microcomputer software (GE Healthcare, Merignac, France).…”

Section: Exercise Protocolmentioning

confidence: 99%

“…It has already been shown that a large proportion (around 70%) of patients with ME/CFS have neuromuscular disorders characterized by exercise-induced alterations of muscle excitability, assessed by decreased amplitude and lengthening of M-waves [14][15][16][17]. The aim of this study was to investigate whether similar exerciseinduced M-wave alterations occur in patients with long-COVID.…”

mentioning

confidence: 96%

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study

2022

Self Cite

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Background Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS. Methods This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests. Results The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured. Conclusions These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms. Trial registration Registered retrospectively.

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“…Chronic fatigue syndrome (CFS) is characterized by inexplicable and persistent fatigue, sleep disturbance, impaired memory or concentration, musculoskeletal pain, and several other somatic complaints (Chi et al, 2016). Several hypotheses have been proposed for the pathogenesis of CFS, including viral infection, immune dysfunction, oxidative stress, and hypothalamic–pituitary–adrenal axis abnormality (Jammes et al, 2020; Johnson et al, 1999; Kempke et al, 2015; Maes et al, 2006; Richards et al, 2007). However, the etiology of CFS remains unclear, and no objective diagnostic methods or effective therapies in conventional medicine are currently available.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics study of the effect of Danggui Buxue Tang on rats with chronic fatigue syndrome

Miao¹,

Li²,

Xiao³

et al. 2022

Biomedical Chromatography

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Danggui Buxue Tang (DBT), a traditional Chinese medicine (TCM) formula for ‘invigorating qi and enriching blood’, has been reported to produce a good effect on chronic fatigue syndrome (CFS). However, the related mechanism remains largely undetermined. This study devised a metabolomics approach with GC–MS combined with pattern recognition to estimate the extent to which DBT alleviated CFS induced by food restriction and force swimming in rats. After 4 weeks of treatment, the endurance capability of rats was significantly better, and the motionless time was significantly shorter in the DBT group than in the CFS model group. Moreover, the activities of superoxide dismutase and glutathione peroxidase increased, whereas the levels of malondialdehyde, interleukin 6, and tumor necrosis factor alpha decreased in the DBT treatment group. Fifteen significantly changed metabolites were observed in the serum of rats with CFS, which was reversed markedly by DBT treatment. Metabolic pathway analysis showed that DBT could possibly alleviate CFS in rats by regulating the biosynthesis of phenylalanine, tyrosine, and tryptophan and the metabolism of glycine, serine, threonine, glycerolipid, glyoxylate, dicarboxylate, and tyrosine. It was observed that the metabolism of glycine, serine, and threonine was most closely related to the improvement in CFS by DBT treatment. This study showed that DBT could improve CFS effectively, and metabolomics was a powerful means to gain insights into the TCM formulas against CFS.

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Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

Cited by 11 publications

References 30 publications

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study

Metabolomics study of the effect of Danggui Buxue Tang on rats with chronic fatigue syndrome

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