title: The effect of lengthening contractions on neuromuscular junction structure in adult and old mice.
abstract: Skeletal muscles of old mice demonstrate a profound inability to regenerate fully following damage. Such a failure could be catastrophic to older individuals where muscle loss is already evident. Degeneration and regeneration of muscle fibres following contraction-induced injury in adult and old mice are well characterised, but little is known about the accompanying changes in motor neurons and neuromuscular junctions (NMJs) following this form of injury although defective re-innervation of muscle following contraction-induced damage has been proposed to play a role in sarcopenia. This study visualised and quantified structural changes to motor neurons and NMJs in Extensor digitorum longus (EDL) muscles of adult and old Thy1-YFP transgenic mice during regeneration following contraction-induced muscle damage. Data demonstrated that the damaging contraction protocol resulted in substantial initial disruption to NMJs in muscles of adult mice, which was reversed entirely within 28 days following damage. In contrast, in quiescent muscles of old mice, ∼15 % of muscle fibres were denervated and ∼80 % of NMJs showed disruption. This proportion of denervated and partially denervated fibres remained unchanged following recovery from contraction-induced damage in muscles of old mice although ∼25 % of muscle fibres were completely lost by 28 days post-contractions. Thus, in old mice, the failure to restore full muscle force generation that occurs following damage does not appear to be due to any further deficit in the percentage of disrupted NMJs, but appears to be due, at least in part, to the complete loss of muscle fibres following damage.
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Vasilaki
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Pollock
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Ifigeneia
authors.initials: I
authors.lastname: Giakoumaki
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Goljanek-Whysall
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Giorgos K
authors.initials: GK
authors.lastname: Sakellariou
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Pearson
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kayani
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.affiliation: MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing, Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK. mdcr02@liverpool.ac.uk.
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000648:ultrastructure*; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000648:ultrastructure; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation* / Q000473:pathology; D009469:Neuromuscular Junction / Q000648:ultrastructure*; D061848:Optical Imaging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D055948:Sarcopenia / Q000473:pathology*; D000070584:Tripartite Motif Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Ageing; Innervation neuromuscular junction; Lengthening contractions; Regeneration; Skeletal muscle