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No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

Lookup NU author(s): Graham Campbell, Dr Amy Reeve, Dr Iryna Ziabreva, Emeritus Professor Doug Turnbull, Dr Don Mahad



Background: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS.Objectives: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease.Methods: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres.Results: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls.Conclusion: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority.

Publication metadata

Author(s): Campbell GR, Reeve AK, Ziabreva I, Reynolds R, Turnbull DM, Mahad DJ

Publication type: Article

Publication status: Published

Journal: Multiple Sclerosis Journal

Year: 2013

Volume: 19

Issue: 14

Pages: 1858-1866

Print publication date: 01/12/2013

Online publication date: 20/06/2013

Acceptance date: 06/04/2013

Date deposited: 04/11/2014

ISSN (print): 1352-4585

ISSN (electronic): 1477-0970

Publisher: Sage


DOI: 10.1177/1352458513490547


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Funder referenceFunder name
Newcastle Healthcare Charity
Newcastle upon Tyne Hospitals NHS charity
Newcastle NIHR Biomedical Research Centre
Wellcome Trust
906919Wellcome Trust Centre for Mitochondrial Research
G0700718Lifelong Health and Wellbeing Initiative