Exercise in patients with multiple sclerosis

Motl, Robert W.; Sandroff, Brian M.; Kwakkel, Gert; Dalgas, Ulrik; Feinstein, Anthony; Heesen, Christoph; Feys, Peter; Thompson, Alan J.

doi:10.1016/s1474-4422(17)30281-8

Cited by 362 publications

(285 citation statements)

References 76 publications

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“…Besides extrinsic induction or activation of Pgc-1α, it can also be induced by intrinsic mechanisms, such as cold exposure or exercise (Lin et al, 2005). Exercise 11 ameliorates the EAE disease course (Klaren et al, 2014;Rossi et al, 2009) and shows several benefits in MS patients (Motl et al, 2017), however the proof of a neuroprotective effect that is mediated by Pgc-1α induction is currently outstanding.…”

Section: Discussionmentioning

confidence: 99%

Enhancing mitochondrial activity in neurons protects against neurodegeneration in CNS inflammation

Rosenkranz

Shaposhnykov

Träger

et al. 2020

Preprint

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Central nervous system (CNS) inflammation in multiple sclerosis (MS) drives neuro-axonal loss resulting in irreversible disability. While transcripts of mitochondrial genes are strongly suppressed in neurons during CNS inflammation, it is unknown whether this results in mitochondrial dysfunction and whether interventions that increase mitochondrial function can rescue neurodegeneration. Here we show that suppression of mitochondrial gene transcripts in inflamed neurons was predominantly affecting genes of the electron transport chain resulting in impaired mitochondrial complex IV activity. This was associated with posttranslational inactivation of the transcriptional co-regulator peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α). Neuronal overexpression of Pgc-1α led to increased numbers of mitochondria, complex IV activity and elevated maximum respiratory capacity. Moreover, Pgc-1αoverexpressing neurons showed a higher mitochondrial membrane potential that related to an improved calcium buffering capacity. Accordingly, neuronal deletion of Pgc-1α aggravated neurodegeneration during experimental autoimmune encephalomyelitis (EAE), while neuronal overexpression of Pgc-1α ameliorated EAE disease course and preserved neurons. Our study provides systemic insights into mitochondrial dysfunction in neurons during inflammation and commends elevation of mitochondrial activity as a promising neuroprotective strategy.

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Section: Discussionmentioning

confidence: 99%

Enhancing mitochondrial activity in neurons protects against neurodegeneration in CNS inflammation

Rosenkranz

Shaposhnykov

Träger

et al. 2020

Preprint

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“…Exercise can be a helpful rehabilitation approach for individuals with MS to reestablish function, endorse wellness, and increase involvement in activities of daily living [11,12,13]. Moreover, accumulating evidence suggests that persons with MS are less physically active than are non-diseased populations [12].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, accumulating evidence suggests that persons with MS are less physically active than are non-diseased populations [12]. …”

Section: Introductionmentioning

confidence: 99%

The Effect of Three Different Strategies Based on Motor Task Performance on Neuromuscular Fatigue in Healthy Men and Men with Multiple Sclerosis

et al. 2018

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Background and objectives: Fatigue during physical activity occurs because of decreased neuromuscular function. The aim of this study was to evaluate the effect of three different strategies based on motor task performance on neuromuscular fatigue in healthy men and men with multiple sclerosis (MS). Materials and Methods: We studied age-matched (18–43 years of age) healthy men (n = 15) and men with MS (n = 9). The inclusion criteria for MS subjects were a Kurtzke Expanded Disability Status Score <4 and a Fatigue Severity Scale Score >5. Both groups performed one of three exercise trials (with at least a 1-week interval between them) of 100 intermittent isometric knee extensions with flexion of 60°. The three different experimental conditions (ECs) were intermittent isometric contraction tasks with constant, predictable, and unpredictable torque target sequences. The variation of maximal voluntary contraction contractions (MVCs) within the strategies was 25%, 50%, and 75%, with a set average of 50%. All of them had a 5 s contraction and a 20 s rest period. The variables were measured: before exercise, after 100 repetitions (100-Reps), and 1 h after exercise. Results: In all EC tasks, the central activation ratio values of healthy and MS subjects were significantly different; however, no significant differences were observed among the EC tasks. No significant differences were seen in electrically induced torque, MVC torque, muscle temperature, subjective sensation of effort, coefficient of variation, or constant and absolute error after 100-Reps and 1 h after exercise between the two groups and in all EC tasks. Conclusions: Men with MS experienced higher central motor fatigue than did healthy men, but this had no effect on the variability, accuracy, or force sensation of the movements performed.

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“…Exercise training has received increasing attention as a putative strategy to target the degenerative component of multiple sclerosis (Motl et al 2017). Some (Kim & Sung 2017), albeit not all (Klaren et al 2016) studies conducted in experimental autoimmune encephalomyelitis (the animal model of MS) have indicated a neuroregenerative effect of exercise.…”

Section: Introductionmentioning

confidence: 99%

Short-term aerobic training does not improve memory functioning in relapsing remitting multiple sclerosis – a randomized controlled trial

Baquet

Hasselmann

Patra

et al. 2018

Preprint

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Background Only few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in MS. Objective and methods This randomized controlled trial aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting MS. The primary outcome was verbal memory (Verbal learning and memory test, VLMT). Patients were randomized to an intervention group (IG) program or a waitlist control group (CG). Patients in the IG exercised according to an individually tailored training schedule (with 2-3 sessions per week for 12 weeks). The primary analysis was carried out using the intention-to-treat (ITT) sample with ANCOVA adjusting for baseline scores. Results 77 RRMS patients were screened and 68 participants randomized (CG n=34; IG n=34). The sample comprised 68% females, had a mean age of 39 years, a mean disease duration of 6.3 years, and a mean EDSS of 1.8. No significant effects were detected in the ITT analysis for the primary endpoint VLMT or any other cognitive measures. Moreover, no significant treatment effects were observed for quality of life, fatigue, or depressive symptoms. Conclusion This study failed to demonstrate beneficial effects of aerobic exercise on cognition in RRMS. The trial was prospectively registered at clinicaltrials.gov (NCT02005237).

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Exercise in patients with multiple sclerosis

Cited by 362 publications

References 76 publications

Enhancing mitochondrial activity in neurons protects against neurodegeneration in CNS inflammation

Enhancing mitochondrial activity in neurons protects against neurodegeneration in CNS inflammation

The Effect of Three Different Strategies Based on Motor Task Performance on Neuromuscular Fatigue in Healthy Men and Men with Multiple Sclerosis

Short-term aerobic training does not improve memory functioning in relapsing remitting multiple sclerosis – a randomized controlled trial

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