Top

Published in:

01-04-2006 | Original Paper

Protein co-expression with axonal injury in multiple sclerosis plaques

Authors: Maria Diaz-Sanchez, Kelly Williams, Gabriele C. DeLuca, Margaret M. Esiri

Published in: Acta Neuropathologica | Issue 4/2006

Abstract

Damage to axons in acute multiple sclerosis (MS) lesions is now well established but the mechanisms of this damage remain obscure. Here we have applied a panel of antibodies that identify cell populations and proteins contained in them with a view to detecting those cells and proteins that are localised particularly closely to damaged axons in acute, sub-acute and border-active MS plaques. Results are expressed semi-quantitatively and graphs produced that show that many of the markers show enhanced expression at sites of axon damage. However, the sharpest increase in expression in relation to axon damage was seen for Calpain I (μ-calpain), inducible nitric oxide synthase and MMP-2, suggesting that these proteins may form part of a group of proteins responsible for the initiation of myelin and/or axon damage seen in MS lesions.

Anthony DC, Ferguson B, Matyzak MK, Miller KM, Esiri MM, Perry VH (1997) Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol 23:406–415CrossRefPubMed

Araujo Couto L, Sampaio Narciso M, Hokoc JN, Blanco Martinez AM (2004) Calpain inhibitor 2 prevents axonal degeneration of opossum optic nerve fibers. J Neurosci Res 77:410–419CrossRefPubMed

Bechtold DA, Yue X, Evans RM, Davies M, Gregson NA, Smith KJ (2005) Axonal protection in experimental autoimmune neuritis by the sodium channel blocking agent flecainide. Brain 128:18–28CrossRefPubMed

Benjamins JA, Nedelkoska L, George EB (2003) Protection of mature oligodendrocytes by inhibitors of caspases and calpains. Neurochem Res 28:143–152CrossRefPubMed

Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Bruck W (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123(Pt 6):1174–1183CrossRefPubMed

Bjartmar C, Wujek JR, Trapp BD (2003) Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 206:165–171CrossRefPubMed

Bo L, Dawson TM, Wesselingh S, Mork S, Choi S, Kong PA, Hanley D, Trapp BD (1994) Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 36:778–786CrossRefPubMed

Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, Sobel RA, Lock C, Karpuj M, Pedotti R, Heller R, Oksenberg JR, Steinman L (2001) The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294:1731–1735CrossRefPubMed

Chandler S, Cossins J, Lury J, Wells G (1996) Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein. Biochem Biophys Res Commun 228:421–429CrossRefPubMed

10.

Cossins JA, Clements JM, Ford J, Miller KM, Pigott R, Vos W, Van der Valk P, De Groot CJ (1997) Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol (Berl) 94:590–598CrossRef

11.

Cuzner ML, Gveric D, Strand C, Loughlin AJ, Paemen L, Opdenakker G, Newcombe J (1996) The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J Neuropathol Exp Neurol 55:1194–1204PubMedCrossRef

12.

Davie CA, Barker GJ, Webb S, Tofts PS, Thompson AJ, Harding AE, McDonald WI, Miller DH (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118(Pt 6):1583–1592PubMedCrossRef

13.

DeLuca GC, Ebers GC, Esiri MM (2004) Axonal loss in multiple sclerosis: a pathological survey of the corticospinal and sensory tracts. Brain 127:1009–1018CrossRefPubMed

14.

De Stefano N, Matthews PM, Antel JP, Preul M, Francis G, Arnold DL (1995) Chemical pathology of acute demyelinating lesions and its correlation with disability. Ann Neurol 38:901–909CrossRefPubMed

15.

De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, Antel JP, Arnold DL (1998) Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121(Pt 8):1469–1477CrossRefPubMed

16.

Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM (2000) Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. Brain 123(Pt 9):1845–1849CrossRefPubMed

17.

Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120(Pt 3):393–399CrossRefPubMed

18.

Filippi M (2001) Linking structural, metabolic and functional changes in multiple sclerosis. Eur J Neurol 8:291–297CrossRefPubMed

19.

Filippi M, Paty DW, Kappos L, Barkhof F, Compston DA, Thompson AJ, Zhao GJ, Wiles CM, McDonald WI, Miller DH (1995) Correlations between changes in disability and T2-weighted brain MRI activity in multiple sclerosis: a follow-up study. Neurology 45:255–260PubMed

20.

Filippi M, Bozzali M, Rovaris M, Gonen O, Kesavadas C, Ghezzi A, Martinelli V, Grossman RI, Scotti G, Comi G, Falini A (2003) Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain 126:433–437CrossRefPubMed

21.

Guo H, Cai CQ, Schroeder RA, Kuo PC (2001) Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol 166:1079–1086PubMed

22.

Hashimoto M, Koda M, Ino H, Murakami M, Yamazaki M, Moriya H (2003) Upregulation of osteopontin expression in rat spinal cord microglia after traumatic injury. J Neurotrauma 20:287–296CrossRefPubMed

23.

Hill KE, Zollinger LV, Watt HE, Carlson NG, Rose JW (2004) Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: distribution, cellular expression and association with myelin damage. J Neuroimmunol 151:171–179CrossRefPubMed

24.

Jansson M, Panoutsakopoulou V, Baker J, Klein L, Cantor H (2002) Cutting edge: attenuated experimental autoimmune encephalomyelitis in eta-1/osteopontin-deficient mice. J Immunol 168:2096–2099PubMed

25.

Kapoor R, Davies M, Blaker PA, Hall SM, Smith KJ (2003) Blockers of sodium and calcium entry protect axons from nitric oxide-mediated degeneration. Ann Neurol 53:174–180CrossRefPubMed

26.

Kim SY, Choi YS, Choi JS, Cha JH, Kim ON, Lee SB, Chung JW, Chun MH, Lee MY (2002) Osteopontin in kainic acid-induced microglial reactions in the rat brain. Mol Cells 13:429–435PubMed

27.

Kim MD, Cho HJ, Shin T (2004) Expression of osteopontin and its ligand, CD44, in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis. J Neuroimmunol 151:78–84CrossRefPubMed

28.

Kornek B, Storch MK, Weissert R, Wallstroem E, Stefferl A, Olsson T, Linington C, Schmidbauer M, Lassmann H (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 157:267–276PubMed

29.

Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Bruck W (2002) Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 125:2202–2212CrossRefPubMed

30.

Lassmann H (2003) Axonal injury in multiple sclerosis. J Neurol Neurosurg Psychiatry 74:695–697CrossRefPubMed

31.

Li X, O’Regan AW, Berman JS (2003) IFN-gamma induction of osteopontin expression in human monocytoid cells. J Interferon Cytokine Res 23:259–265CrossRefPubMed

32.

Lindberg RL, De Groot CJ, Montagne L, Freitag P, van der Valk P, Kappos L, Leppert D (2001) The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 124:1743–1753CrossRefPubMed

33.

Liu JS, Zhao ML, Brosnan CF, Lee SC (2001) Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 158:2057–2066PubMed

34.

Losseff NA, Webb SL, O’Riordan JI, Page R, Wang L, Barker GJ, Tofts PS, McDonald WI, Miller DH, Thompson AJ (1996) Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119(Pt 3):701–708PubMedCrossRef

35.

Lovas G, Szilagyi N, Majtenyi K, Palkovits M, Komoly S (2000) Axonal changes in chronic demyelinated cervical spinal cord plaques. Brain 123(Pt 2):308–317CrossRefPubMed

36.

Maeda A, Sobel RA (1996) Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol 55:300–309PubMedCrossRef

37.

Morris CS, Esiri MM, Sprinkle TJ, Gregson N (1994) Oligodendrocyte reactions and cell proliferation markers in human demyelinating diseases. Neuropathol Appl Neurobiol 20:272–281PubMedCrossRef

38.

Mycko MP, Papoian R, Boschert U, Raine CS, Selmaj KW (2003) cDNA microarray analysis in multiple sclerosis lesions: detection of genes associated with disease activity. Brain 126:1048–1057CrossRefPubMed

39.

Newman TA, Woolley ST, Hughes PM, Sibson NR, Anthony DC, Perry VH (2001) T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases. Brain 124:2203–2214CrossRefPubMed

40.

Peterson J, Kidd G, Trapp BD (2005) Axonal degeneration in multiple sclerosis: the histopathological evidence. In: Waxman S (ed) Multiple sclerosis as a neuronal disease. Elsevier, New York, pp. 165–184CrossRef

41.

Petzold A, Eikelenboom MJ, Keir G, Grant D, Lazeron RH, Polman CH, Uitdehaag BM, Thompson EJ, Giovannoni G (2005) Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study. J Neurol Neurosurg Psychiatry 76:206–211CrossRefPubMed

42.

Raine CS (1994) The Dale E. McFarlin Memorial Lecture: the immunology of the multiple sclerosis lesion. Ann Neurol 36(Suppl):S61–S72CrossRefPubMed

43.

Ray SK, Banik NL (2003) Calpain and its involvement in the pathophysiology of CNS injuries and diseases: therapeutic potential of calpain inhibitors for prevention of neurodegeneration. Curr Drug Targets CNS Neurol Disord 2:173–189CrossRefPubMed

44.

Redford EJ, Kapoor R, Smith KJ (1997) Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain 120(Pt 12):2149–2157CrossRefPubMed

45.

Rodriguez M (2003) A function of myelin is to protect axons from subsequent injury: implications for deficits in multiple sclerosis. Brain 126:751–752CrossRefPubMed

46.

Rosenberg GA (2002) Matrix metalloproteinases and neuroinflammation in multiple sclerosis. Neuroscientist 8:586–595CrossRefPubMed

47.

Saatman KE, Abai B, Grosvenor A, Vorwerk CK, Smith DH, Meaney DF (2003) Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice. J Cereb Blood Flow Metab 23:34–42CrossRefPubMed

48.

Saido TC, Sorimachi H, Suzuki K (1994) Calpain: new perspectives in molecular diversity and physiological–pathological involvement. FASEB J 8:814–822PubMed

49.

Selvaraju R, Bernasconi L, Losberger C, Graber P, Kadi L, Avellana-Adalid V, Picard-Riera N, Van Evercooren AB, Cirillo R, Kosco-Vilbois M, Feger G, Papoian R, Boschert U (2004) Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro. Mol Cell Neurosci 25:707–721CrossRefPubMed

50.

Shields DC, Schaecher KE, Saido TC, Banik NL (1999) A putative mechanism of demyelination in multiple sclerosis by a proteolytic enzyme, calpain. Proc Natl Acad Sci USA 96:11486–11491CrossRefPubMed

51.

Shin SL, Cha JH, Chun MH, Chung JW, Lee MY (1999) Expression of osteopontin mRNA in the adult rat brain. Neurosci Lett 273:73–76CrossRefPubMed

52.

da Silva RP, Gordon S (1999) Phagocytosis stimulates alternative glycosylation of macrosialin (mouse CD68), a macrophage-specific endosomal protein. Biochem J 338(Pt 3):687–694CrossRefPubMed

53.

Sinclair C, Mirakhur M, Kirk J, Farrell M, McQuaid S (2005) Up-regulation of osteopontin and alphaBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays. Neuropathol Appl Neurobiol 31:292–303CrossRefPubMed

54.

Smith KJ (2005) Nitric oxide and axonal patholophysiology. In: Waxman S (eds) Multiple sclerosis as a neuronal disease. Elsevier, New York, pp. 255–273CrossRef

55.

Smith KJ, Kapoor R, Felts PA (1999) Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol 9:69–92PubMed

56.

Smith KJ, Kapoor R, Hall SM, Davies M (2001) Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol 49:470–476CrossRefPubMed

57.

Steinman L, Martin R, Bernard C, Conlon P, Oksenberg JR (2002) Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Annu Rev Neurosci 25:491–505CrossRefPubMed

58.

Stys PK (2004) White matter injury mechanisms. Curr Mol Med 4:113–130CrossRefPubMed

59.

Takahashi F, Takahashi K, Maeda K, Tominaga S, Fukuchi Y (2000) Osteopontin is induced by nitric oxide in RAW 264.7 cells. IUBMB Life 49:217–221CrossRefPubMed

60.

Touil T, Deloire-Grassin MS, Vital C, Petry KG, Brochet B (2001) In vivo damage of CNS myelin and axons induced by peroxynitrite. Neuroreport 12:3637–3644CrossRefPubMed

61.

Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285CrossRefPubMed

62.

Weber GF, Ashkar S, Glimcher MJ, Cantor H (1996) Receptor–ligand interaction between CD44 and osteopontin (Eta-1). Science 271:509–512PubMedCrossRef

Title: Protein co-expression with axonal injury in multiple sclerosis plaques
Authors: Maria Diaz-Sanchez
Kelly Williams
Gabriele C. DeLuca
Margaret M. Esiri
Publication date: 01-04-2006
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-006-0045-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Protein co-expression with axonal injury in multiple sclerosis plaques

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2006

Kindled seizures enhance young neuron survival in the adult rat dentate gyrus

Characterization and application of polyclonal antibodies that specifically recognize JC virus large T antigen

Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred

Axonopathy in an APP/PS1 transgenic mouse model of Alzheimer’s disease

GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus

Argyrophilic grain disease: frequency and neuropathology in centenarians