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Effect of partial denervation mitochondrial ROS generation in skeletal muscle
Author(s) -
Pollock Natalie,
Staunton Caroline Amy,
Vasilaki Aphrodite,
McArdle Anne,
Jackson Malcolm
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.764.1
Subject(s) - denervation , skeletal muscle , anatomy , mitochondrion , neuromuscular junction , extensor digitorum longus muscle , ultrastructure , chemistry , biology , microbiology and biotechnology , neuroscience
Dramatic changes in mitochondrial generation of hydrogen peroxide (H 2 O 2 ) are observed in the skeletal muscle of rodents following experimental nerve transection. The consequences of this denervation are well documented. We have hypothesised that denervation of even a limited number of fibers, such as that observed in muscles during ageing, could influence mitochondrial H 2 O 2 generation by both denervated and innervated fibers throughout the muscle. Thy1‐YFP mice (expressing YFP in neuronal cells only) underwent surgical transection of one of the 3 nerve branches entering the anterior tibialis (AT) muscle. Generation of H 2 O 2 by mitochondria in permeablised fibers with intact mitochondria from 4 different regions of the AT muscle was assessed using Amplex Red. Confocal microscopy of the excised muscle allowed us to visually track and map the morphological changes in both muscle and nerve which accompanied the post‐surgical changes in H 2 O 2 generation. Following partial denervation, oxidation of Amplex red was increased by 40–70 fold in the bundles of fibers from all regions of the AT muscle. This increase was comparable to those observed in fully denervated muscles in our previous experiments. Imaging techniques have demonstrated that NMJ morphology following partial denervation is variable and undergoes rapid changes. At 24 hrs following surgery, the site of surgical denervation is clearly identifiable by the loss of nerve endplates, with no evidence of post‐synaptic changes. By 7 days post‐surgery, the morphological status of the NMJ's is highly variable across the entirety of the muscle. Cross‐sectional area analysis has revealed that even partial denervation is sufficient to cause muscle fibre atrophy, with no clear correlation between the site of initial injury and fibre cross‐sectional area. Taken together, these data show that mitochondria in innervated muscle fibers are affected by denervation of adjacent fibers and contribute to the increased H 2 O 2 generation. Thus data support our hypothesis that loss of innervation in some muscle fibres is sufficient to disrupt the regulation of mitochondrial H 2 O 2 generation with consequences for the entire muscle, an effect which may be mirrored in sarcopenia. Support or Funding Information Supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC).