title: Abnormalities of satellite cells function in amyotrophic lateral sclerosis.
abstract: Abstract Amyotrophic lateral sclerosis (ALS) is characterized by progressive denervation leading to muscle atrophy prevented, during the early phase, by compensatory reinnervation. Little is known about muscle fibre regeneration capacity in ALS. We have carried out in vivo and in vitro investigation of skeletal muscle in ALS. Seven ALS patients underwent a deltoid muscle biopsy. Immunohistochemical analysis revealed various degrees of denervation- and reinnervation-related changes in the ALS muscle biopsies including satellite cells (SCs) activation and regenerating fibres. Only 3/7 primary cultures of ALS muscle cells were successfully established and had sufficient myogenicity, as assessed by desmin positivity, to be used without further purification. This was in contrast with the cultures derived from control muscles, predominantly desmin-positive cells. Although capable to proliferate in vitro, ALS-derived SCs presented an abnormal senescent-like morphology. Markers of senescence, including senescent-associated (SA)-βGal activity and p16 expression, were increased. Furthermore, ALS-derived SCs were also unable to fully differentiate in vitro as shown by abnormal myotubes morphology and reduced MHC isoform expression, compared to control myotubes. Our study suggests that SC function is altered in ALS. This could limit the efficacy of compensatory processes and therefore could contribute to the progression of muscle atrophy and weakness.
authors.affiliation: Assistance Publique Hôpitaux de Paris, Département des Maladies du Système Nerveux, Centre de référence maladies rares SLA, Hôpital Pitié-Salpêtrière, France. pierre-francois.pradat@psl.aphp.fr
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.forename: Aude
authors.initials: A
authors.lastname: Barani
authors.forename: Julia
authors.initials: J
authors.lastname: Wanschitz
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
authors.forename: Anne
authors.initials: A
authors.lastname: Bigot
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Gaelle
authors.initials: G
authors.lastname: Bruneteau
authors.forename: François
authors.initials: F
authors.lastname: Salachas
authors.forename: Timothée
authors.initials: T
authors.lastname: Lenglet
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D003893:Desmin / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000473:pathology* / Q000502:physiology*
chemical_list: D015415:Biomarkers; D003893:Desmin; D018995:Myosin Heavy Chains