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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

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Abstract

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

URL: http://dx.doi.org/10.1177/1352458513490547

DOI: 10.1177/1352458513490547


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Funding

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

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