title: A role for caspase-1 and -3 in the pathology of experimental allergic encephalomyelitis : inflammation versus degeneration.
abstract: Axonal loss, already present in the acute and first relapse phases of experimental allergic encephalomyelitis (EAE) in the ABH mouse, only becomes apparent in the third relapse in the interleukin-12 model of relapsing EAE in the Lewis rat. Caspase-1 immunostaining in the spinal cord of Lewis rats was mainly localized to inflammatory cuffs with the greatest proportion of active caspase-1-positive cells detected during the first and second relapses, correlating with enzyme activity and protein on Western blots. However, in the spinal cord of ABH mice during acute EAE, caspase-1 immunostaining was localized both on inflammatory and neuronal cells, again correlating with enzyme activity and protein production. In contrast, caspase-3 expression in the spinal cord of Lewis rats did not increase significantly until the third relapse when inflammatory and neuronal cells and axons became positive in line with a significant increase in caspase activity. In ABH mice active caspase-3 was already immunolocalized on axons and apoptotic neurons in the spinal cord during the acute stage of EAE. Because caspase-3 is a downstream cell death signal it may be possible to reduce apoptosis by selectively blocking caspase-3 and therefore provide a therapeutic target for EAE and potentially, multiple sclerosis.
authors.affiliation: Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Ahmed
authors.forename: Anne I
authors.initials: AI
authors.lastname: Doward
authors.forename: Gareth
authors.initials: G
authors.lastname: Pryce
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Taylor
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Pocock
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.forename: M Louise
authors.initials: ML
authors.lastname: Cuzner
mesh_terms: D000818:Animals; D001369:Axons / Q000201:enzymology / Q000473:pathology; D020170:Caspase 1 / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D053938:DNA Fragmentation; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology
chemical_list: C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1