Muscle carnosine in experimental autoimmune encephalomyelitis and multiple sclerosis

Keytsman, Charly; Blancquaert, Laura; Wens, Inez; Missine, Maarten; Noten, Pieter Van; Vandenabeele, Frank; Derave, Wim; Eijnde, Bert O.

doi:10.1016/j.msard.2018.02.013

Cited by 13 publications

(14 citation statements)

References 54 publications

(97 reference statements)

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“…Previous studies on the effects of ET on EAE yielded variable results. Clinical outcomes ranged from worsening of symptoms, no effect on clinical severity, to disease attenuation, as indicated by delayed onset and peak of disease and even overall attenuation of the clinical course . The inconsistencies in these studies likely derived from variations in training modes (running, swimming) and protocols (intensity, speed, volume, duration) that were employed.…”

Section: Discussionmentioning

confidence: 99%

Exercise intensity‐dependent immunomodulatory effects on encephalomyelitis

Fainstein

Tyk

Touloumi

et al. 2019

Ann Clin Transl Neurol

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Background Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity‐dependent effects of ET on the systemic immune system in EAE remain undefined. Objective (1) To compare the systemic immune modulatory effects of moderate versus high‐intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression. Methods Healthy mice performed moderate or high‐intensity treadmill running programs. Proteolipid protein (PLP)‐induced transfer EAE was utilized to examine ET effects specifically on the systemic immune system. Lymph node (LN)‐T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed, by clinical assessment and histopathological analysis. LN‐T cells derived from donor trained versus sedentary PLP‐immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real‐time PCR. T cell‐dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli‐induced acute peritonitis were examined. Results High‐intensity training in healthy donor mice induced significantly greater inhibition than moderate‐intensity training on proliferation and generation of encephalitogenic T cells in response to PLP‐immunization, and on EAE severity upon their transfer into recipient mice. High‐intensity training also inhibited LN‐T cell proliferation in response to ovalbumin immunization. E. coli bacterial counts and dissemination were not affected by training. Interpretation High‐intensity training induces superior effects in preventing autoimmunity in EAE, but does not alter immune responses to E. coli infection.

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Section: Discussionmentioning

confidence: 99%

Exercise intensity‐dependent immunomodulatory effects on encephalomyelitis

Fainstein

Tyk

Touloumi

et al. 2019

Ann Clin Transl Neurol

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“…Forced treadmill exercise paradigm has been used on EAE animals with conflicting results regarding the clinical score. Therefore, worsening of symptoms ( 24 ), no effect on disability ( 25 – 27 ), delayed day of peak disease ( 28 ) or of onset of disease ( 29 ) and even a global amelioration of clinical signs ( 30 , 31 ) has been demonstrated on EAE animals that have been exercised on treadmill. Nevertheless, different EAE models, as well as different volume, intensity and duration of exercise, may affect final conclusions.…”

Section: Discussionmentioning

confidence: 99%

Regular Exercise Modifies Histopathological Outcomes of Pharmacological Treatment in Experimental Autoimmune Encephalomyelitis

Bernardes

Oliveira

2018

Front. Neurol.

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Background: Although it has been suggested that healthier lifestyle may optimize effects of the immunomodulation drugs for treating multiple sclerosis (MS), the knowledge regarding this kind of interactions is limited.Objective: The aim of the present study was to investigate the effects of treadmill exercise in combination with pharmacological treatment in an animal model for MS.Methods: C57BL/6J female mice were subjected to daily treadmill exercise for 4 weeks before immunization and 6 weeks before clinical presentation of disease. Dimethyl fumarate (DMF) or glatiramer acetate (GA) were administered after the first clinical relapse. Histopathological analyses were carried out in the lumbar spinal cord at peak disease and at 1 or 14 days post-treatment (dpt).Results: Exercised-GA treated animals demonstrated decreased astrocytic response in the spinal dorsal horn with an improvement in the paw print pressure. Exercised-DMF treated animals showed an increased microglial/macrophage response on both ventral and dorsal horn that were associated with clinical improvement and synaptic motoneuron inputs density.Conclusion: The present data suggest that prior regular exercise can modify the effects of pharmacological treatment administered after the first relapse in a murine model for MS.

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“…Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the CNS with progressive demyelinization [93]. In an animal model of multiple sclerosis, muscle carnosine levels were decreased and were not restored by exercise, which possibly mirrors altered muscular functions in MS [94]. Another animal study reported delayed onset of symptoms in exercising rats following the induction of MS [95].…”

Section: Animal Studies Of the Role Of Carnosine In Brain-related mentioning

confidence: 99%

“…Patients with multiple sclerosis have increased plasma histidine and decreased alanine levels compared with patients with other inflammatory demyelinating diseases [147]. Reductions in serum carnosinase activity have also been proposed as a potential explanation for the impaired exercise capacity, excessive post-exercise fatigue, and reduced muscle contractile function that are usually present in multiple sclerosis [94,148]. It is, therefore, not surprising that individuals with multiple sclerosis had reduced skeletal muscle carnosine content and 10-day exercise training did not restore it [94].…”

Section: Human Observational Studies Of the Role Of Carnosine In Bmentioning

confidence: 99%

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence

Schön

Mousa²,

Berk

et al. 2019

Nutrients

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Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.

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Muscle carnosine in experimental autoimmune encephalomyelitis and multiple sclerosis

Abstract: Muscle carnosine concentrations in an animal MS model and MS patients are substantially reduced. In EAE exercise therapy does not restore this.

Cited by 13 publications

References 54 publications

Exercise intensity‐dependent immunomodulatory effects on encephalomyelitis

Exercise intensity‐dependent immunomodulatory effects on encephalomyelitis

Regular Exercise Modifies Histopathological Outcomes of Pharmacological Treatment in Experimental Autoimmune Encephalomyelitis

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence

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