Mitochondrial defects in acute multiple sclerosis lesions.
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 Balo's 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.
Mahad
Don
D
The Mitochondrial Research Group, University of Newcastle upon Tyne, UK.
Ziabreva
Iryna
I
Lassmann
Hans
H
Turnbull
Douglas
D
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000150:complications / Q000378:metabolism; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009103:Multiple Sclerosis / Q000150:complications* / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism
D024101:Mitochondrial Proteins; D003576:Electron Transport Complex IV