title: Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis.
abstract: Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers, neurodegenerative factors, myogenic factors, cell cycle determinants, and inflammatory markers. Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting.
authors.affiliation: Institute of Clinical Research, Clinical Pathology, SDU Muscle Research Cluster, University of Southern Denmark and Odense University Hospital, J. B. Winsløw Vej 15, 3, 5000 Odense C, Denmark; Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Jensen
authors.affiliation: Institute of Clinical Research, Clinical Pathology, SDU Muscle Research Cluster, University of Southern Denmark and Odense University Hospital, J. B. Winsløw Vej 15, 3, 5000 Odense C, Denmark.
authors.forename: L H
authors.initials: LH
authors.lastname: Jørgensen
authors.affiliation: Institute of Clinical Research, The Orthopaedic Research Unit, University of Southern Denmark and Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark.
authors.forename: R D
authors.initials: RD
authors.lastname: Bech
authors.affiliation: Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: U
authors.initials: U
authors.lastname: Frandsen
authors.affiliation: Institute of Clinical Research, Clinical Pathology, SDU Muscle Research Cluster, University of Southern Denmark and Odense University Hospital, J. B. Winsløw Vej 15, 3, 5000 Odense C, Denmark.
authors.forename: H D
authors.initials: HD
authors.lastname: Schrøder
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D017570:MyoD Protein / Q000096:biosynthesis* / Q000235:genetics; D051763:PAX7 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human