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Background Muscle carnosine is related to contractile function (Ca ++ handling) and buffering of exercise–induced acidosis. As these muscular functions are altered in Multiple Sclerosis (MS) it is relevant to understand muscle carnosine levels in MS. Methods Tibialis anterior muscle carnosine was measured in an animal MS model (EAE, experimental autoimmune encephalomyelitis, n = 40) and controls (CON, n = 40) before and after exercise training (EAE EX , CON EX , 10d, 1 h/d, 24 m/min treadmill running) or sedentary conditions (EAE SED , CON SED ). Human m. vastus lateralis carnosine of healthy controls (HC, n = 22) and MS patients (n = 24) was measured. Results EAE muscle carnosine levels were decreased (p < .0001) by ~ 40% to ~ 64% at 10d and 17d following EAE induction (respectively) regardless of exercise (p = .823). Similarly, human MS muscle carnosine levels were decreased (− 25%, p = .03). Conclusion Muscle carnosine concentrations in an animal MS model and MS patients are substantially reduced. In EAE exercise therapy does not restore this. [ABSTRACT FROM AUTHOR]

Background Multiple sclerosis (MS) is associated with elevated cardiovascular mortality. To prevent this a better understanding of their CVD risk factors and interrelations is necessary. Methods MS patients (n = 52) and healthy controls (HC, n = 24) were matched for age, height, weight, body mass index and physical activity. Body composition, resting blood pressure (BP), resting heart rate (HR), glucose tolerance, HbA1c, blood lipids (HDL, LDL, total cholesterol, triglyceride concentrations) and c-reactive protein concentrations were analyzed. Regression analyses identified independent CVD risk factors and their interrelations in MS. Results In MS and compared to HC, fat mass (25.1 ± 1.2 kg vs. 17.9 ± 1 kg), fat percentage (33.8 ± 1.2% vs. 28.4 ± 1.5%), systolic (130 ± 1.8 mmHg vs. 120 ± 2.9 mmHg) and diastolic (79 ± 1.1 mmHg vs. 71 ± 1.9 mmHg) BP, resting HR (72 ± 1.4 bpm vs. 60 ± 2 bpm), blood triglycerides (113.8 ± 8.6 mg/dl vs. 98.2 ± 17.4 mg/dl), fasting (13.5 ± 2.9 mU/l vs. 7.2 ± 0.8 mU/l) and 2 h insulin (71.9 ± 12.5 mU/l vs. 35.8 ± 8.1 mU/l), 2 h glucose (6.3 ± 0.5 mmol/l vs. 4.8 ± 0.5 mmol/l) and HOMA index (3.7 ± 1.1 vs. 1.7 ± 0.2) were significantly (p < 0.05) elevated. Total cholesterol, blood HDL and LDL concentrations did nog differ between groups (p < 0.05). Regression analyses indicated that MS is independently associated with elevated fat mass/percentage, systolic and diastolic BP and HR and in MS fat mass appears to be an independent contributor of the other measured CVD risk factors in MS. Conclusion Persons with MS have an increased risk for CVD and fat mass appears to be an important risk factor. Therefore, normalizing whole body fat should be an essential part of MS treatment. [ABSTRACT FROM AUTHOR]

Patients with multiple sclerosis (pwMS) experience muscle weakness and lowered muscle oxidative capacity. To explore the etiology for the development of such muscle phenotype we studied skeletal muscle adenosine monophosphate (AMP)-activated protein kinase phosphorylation (phospho-AMPKα, governing mitochondrial biogenesis) and mammalian target of rapamycin phosphorylation (phospho-mTOR, governing myofibrillar biogenesis) in pwMS. After assessment of body composition, muscle strength, exercise tolerance, and muscle fiber type, muscle phospho-AMPKα and phospho-mTOR were assessed in 14 pwMS and 10 healthy controls (part 1). Next, an endurance exercise bout was executed by 9 pwMS and 7 healthy subjects, with assessment of changes in muscle phospho-AMPKα and phospho-mTOR (part 2). Increased basal muscle phospho-AMPKα and phospho-mTOR were present in MS ( P < 0.01) and independently related to MS. Correlations between muscle phospho-AMPKα or phospho-mTOR and whole-body fat mass, peak oxygen uptake, and expanded disability status scale ( P < 0.05) were found. After endurance exercise muscle phospho-AMPKα and phospho-mTOR remained increased in pwMS ( P < 0.01). Muscle signaling cascades for mitochondrial and myofibrillar biogenesis are altered in MS and related to the impairment and disability level. These findings indicate a link between muscle signaling cascades and the level of disability and impairment, and thus may open a new area for the development of novel therapies for peripheral muscle impairment in MS. [ABSTRACT FROM AUTHOR]