title: Oxidative injury in multiple sclerosis cerebellar grey matter.
abstract: Cerebellar dysfunction is a significant contributor to disability in multiple sclerosis (MS). Both white matter (WM) and grey matter (GM) injury occurs within MS cerebellum and, within GM, demyelination, inflammatory cell infiltration and neuronal injury contribute to on-going pathology. The precise nature of cerebellar GM injury is, however, unknown. Oxidative stress pathways with ultimate lipid peroxidation and cell membrane injury occur extensively in MS and the purpose of this study was to investigate these processes in MS cerebellar GM. Post-mortem human cerebellar GM from MS and control subjects was analysed immunohistochemically, followed by semi-quantitative analysis of markers of cellular injury, lipid peroxidation and anti-oxidant enzyme expression. We have shown evidence for reduction in myelin and neuronal markers in MS GM, coupled to an increase in expression of a microglial marker. We also show that the lipid peroxidation product 4-hydroxynonenal co-localises with myelin and its levels negatively correlate to myelin basic protein levels. Furthermore, superoxide dismutase (SOD1 and 2) enzymes, localised within cerebellar neurons, are up-regulated, yet the activation of subsequent enzymes responsible for the detoxification of hydrogen peroxide, catalase and glutathione peroxidase are relatively deficient. These studies provide evidence for oxidative injury in MS cerebellar GM and further help define disease mechanisms within the MS brain.
authors.affiliation: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK. Electronic address: Kevin.Kemp@bristol.ac.uk.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kemp
authors.affiliation: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: Juliana
authors.initials: J
authors.lastname: Redondo
authors.affiliation: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hares
authors.affiliation: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Rice
authors.affiliation: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Scolding
authors.affiliation: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Wilkins
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000378:metabolism; D066127:White Matter / Q000378:metabolism / Q000473:pathology; D000099156:Superoxide Dismutase 2
chemical_list: D000447:Aldehydes; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C499048:MBP protein, human; C000606290:SOD1 protein, human; C027576:4-hydroxy-2-nonenal
keywords: Anti-oxidants; Cerebellum; Grey matter; Multiple sclerosis; Oxidative stress; Peroxidation