Mitochondrial DNA deletions and depletion within paraspinal muscles

G. R. Campbell, A. Reeve, I. Ziabreva, T. M. Polvikoski, R. W. Taylor, R. Reynolds, D. M. Turnbull and D. J. Mahad (2013) Neuropathology and Applied Neurobiology 39, 377–389 Mitochondrial DNA deletions and depletion within paraspinal muscles Aims: Although mitochondrial abnormalities have been reported within paraspinal muscles in patients with axial weakness and neuromuscular disease as well as with ageing, the basis of respiratory deficiency in paraspinal muscles is not known. This study aimed to determine the extent and basis of respiratory deficiency in paraspinal muscles from cases undergoing surgery for degenerative spinal disease and post mortem cases without a history of spinal disease, where age‐related histopathological changes were previously reported. Methods: Cervical and lumbar paraspinal muscles were obtained peri‐operatively from 13 patients and from six post mortem control cases (age range 18–82 years) without a neurological disease. Sequential COX/SDH (mitochondrial respiratory chain complex IV/complex II) histochemistry was performed to identify respiratory‐deficient muscle fibres (lacking complex IV with intact complex II activity). Real‐time polymerase chain reaction, long‐range polymerase chain reaction and sequencing were used to identify and characterize mitochondrial DNA (mtDNA) deletions and determine mtDNA copy number status. Mitochondrial respiratory chain complex subunits were detected by immunohistochemistry. Results: The density of respiratory‐deficient fibres increased with age. On average, 3.96% of fibres in paraspinal muscles were respiratory‐deficient (range 0–10.26). Respiratory deficiency in 36.8% of paraspinal muscle fibres was due to clonally expanded mtDNA deletions. MtDNA depletion accounted for further 13.5% of respiratory deficiency. The profile of immunohistochemically detected subunits of complexes was similar in respiratory‐deficient fibres with and without mtDNA deletions or mtDNA depletion. Conclusions: Paraspinal muscles appeared to be particularly susceptible to age‐related mitochondrial respiratory chain defects. Clonally expanded mtDNA deletions and focal mtDNA depletion may contribute towards the development of age‐related postural abnormalities.