title: Altered signaling for mitochondrial and myofibrillar biogenesis in skeletal muscles of patients with multiple sclerosis.
abstract: 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.
authors: REVAL-Rehabilitation Research Center, BIOMED-Biomedical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium; Heart Centre Hasselt, Jessa Hospital, Hasselt, Belgium. Electronic address: Dominique.hansen@uhasselt.be.
authors: Dominique
authors: D
authors: Hansen
authors: REVAL-Rehabilitation Research Center, BIOMED-Biomedical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Inez
authors: I
authors: Wens
authors: REVAL-Rehabilitation Research Center, BIOMED-Biomedical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Frank
authors: F
authors: Vandenabeele
authors: REVAL-Rehabilitation Research Center, BIOMED-Biomedical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Kenneth
authors: K
authors: Verboven
authors: REVAL-Rehabilitation Research Center, BIOMED-Biomedical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Bert O
authors: BO
authors: Eijnde
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009210:Myofibrils / Q000378:metabolism; D010766:Phosphorylation; D010807:Physical Endurance / Q000502:physiology; D011446:Prospective Studies; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D057170:Translational Research, Biomedical
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases