Oxidative Injury and Iron Redistribution Are Pathological Hallmarks of Marmoset Experimental Autoimmune Encephalomyelitis.
Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE lesion-associated liberation of iron (due to loss of iron-containing myelin) was associated with altered expression of the iron metabolic markers FtH1, lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative damage markers in inflammatory lesions indicates that the enhanced antioxidant enzyme expression could not counteract reactive oxygen and nitrogen species-induced cellular damage, as is also observed in MS brains. This study demonstrates that oxidative injury and aberrant iron distribution are prominent pathological hallmarks of marmoset EAE thus making this model suitable for therapeutic intervention studies aimed at reducing oxidative stress and associated iron dysmetabolism.
['Dunham|Jordon|J|', 'Bauer|Jan|J|', 'Campbell|Graham R|GR|', 'Mahad|Don J|DJ|', 'van Driel|Nikki|N|', 'van der Pol|Susanne M A|SMA|', "'t Hart|Bert A|BA|", 'Lassmann|Hans|H|', 'Laman|Jon D|JD|', 'van Horssen|Jack|J|', 'Kap|Yolanda S|YS|']
D000818:Animals D002144:Callithrix D003711:Demyelinating Diseases D004681:Encephalomyelitis, Autoimmune, Experimental D005260:Female D018840:HSP70 Heat-Shock Proteins D007150:Immunohistochemistry D007501:Iron D008297:Male D009186:Myelin Sheath D019255:NADPH Oxidases D052247:Nitric Oxide Synthase Type II D019159:Nonheme Iron Proteins D018384:Oxidative Stress D013482:Superoxide Dismutase D014018:Tissue Distribution
Marmoset Multiple sclerosis Experimental autoimmune encephalomyelitis (EAE) Neurodegeneration Reactive oxygen species