Mitochondrial defects in acute multiple sclerosis lesions

Don Mahad, Iryna Ziabreva, Hans Lassmann*, Douglas Turnbull

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple sclerosis is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the CNS. The structural and immunopathological patterns of demyelination suggest that different immune mechanisms may be involved in tissue damage. In a subtype of lesions, which are mainly found in patients with acute fulminant multiple sclerosis with Balos type concentric sclerosis and in a subset of early relapsing remitting multiple sclerosis, the initial myelin changes closely resemble those seen in white matter stroke (WMS), suggesting a hypoxia-like tissue injury. Since mitochondrial injury may be involved in the pathogenesis of such lesions, we analysed a number of mitochondrial respiratory chain proteins in active lesions from acute multiple sclerosis and from WMS using immunohistochemistry. Functionally important defects of mitochondrial respiratory chain complex IV [cytochrome c oxidase (COX)] including its catalytic component (COX-I) are present in Pattern III but not in Pattern II multiple sclerosis lesions. The lack of immunohistochemically detected COX-I is apparent in oligodendrocytes, hypertrophied astrocytes and axons, but not in microglia. The profile of immunohistochemically detected mitochondrial respiratory chain complex subunits differs between multiple sclerosis and WMS. The findings suggest that hypoxia-like tissue injury in Pattern III multiple sclerosis lesions may be due to mitochondrial impairment.

Original languageEnglish
Pages (from-to)1722-1735
Number of pages14
JournalBrain
Volume131
Issue number7
DOIs
Publication statusPublished - Jul 2008

Keywords

  • MYELIN-ASSOCIATED GLYCOPROTEIN
  • WHITE-MATTER
  • PERSISTENT INHIBITION
  • multiple sclerosis
  • RESPIRATORY-CHAIN
  • ENCODED SUBUNITS
  • CYTOCHROME-C-OXIDASE
  • mitochondria
  • NITRIC-OXIDE
  • COMPLEX-I
  • NEURODEGENERATIVE DISEASES
  • cytochrome c oxidase
  • CULTURED HUMAN-CELLS
  • Pattern III lesion

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