Skip to main content
SpringerLink
Log in

Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

In the pathogenesis of multiple sclerosis (MS), oligodendrocytes and its myelin sheaths are thought to be the primary target of destruction. The mechanism leading to oligodendrocyte injury and demyelination is still elusive. Oligodendrocytes are maintaining up to 50 internodes of myelin, which is an extraordinary metabolic demand. This makes them one of the most vulnerable cell types in the central nervous system (CNS), and even small insults can lead to oligodendrocyte impairment, demyelination, and axonal dysfunction. For this reason, oligodendrocytes are viewed as more or less the “lame ducks” of the CNS who can easily become victims. However, recent data demonstrate that this perception possibly needs to be revised. The latest data suggest that oligodendrocytes may also act as “fierce creatures,” influencing the surrounding cells in many ways to preserve its own, as well as their function, allowing sustained functionality of the CNS upon an attack. In this review, the concept of “reactive or activated oligodendrocyte” is introduced, describing alterations in oligodendrocytes which are either protective mechanisms allowing survival in otherwise lethal environment or influence and possibly modulate the ongoing inflammation. Although “harnessed”, oligodendrocytes might actively modulate and shape their environment and be part of the immune privilege of the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aboul-Enein, F., Rauschka, H., Kornek, B., Stadelmann, C., Stefferl, A., Bruck, W., et al. (2003). Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases. Journal of Neuropathology and Experimental Neurology, 62, 25–33.

    PubMed  CAS  Google Scholar 

  • Babbe, H., Roers, A., Waisman, A., Lassmann, H., Goebels, N., Hohlfeld, R., et al. (2000). Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. Journal of Experimental Medicine, 192, 393–404.

    PubMed  CAS  Google Scholar 

  • Balabanov, R., Strand, K., Goswami, R., McMahon, E., Begolka, W., Miller, S. D., et al. (2007). Interferon-gamma-oligodendrocyte interactions in the regulation of experimental autoimmune encephalomyelitis. Journal of Neuroscience, 27, 2013–2024.

    PubMed  CAS  Google Scholar 

  • Barnett, M. H., & Prineas, J. W. (2004). Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion. Annals of Neurology, 55, 458–468.

    PubMed  Google Scholar 

  • Becher, B., Barker, P. A., Owens, T., & Antel, J. P. (1998). CD95-CD95L: Can the brain learn from the immune system? Trends in Neurosciences, 21, 114–117.

    PubMed  CAS  Google Scholar 

  • Becher, B., Prat, A., & Antel, J. P. (2000). Brain-immune connection: Immuno-regulatory properties of CNS-resident cells. Glia, 29, 293–304.

    PubMed  CAS  Google Scholar 

  • Berger, T., Weerth, S., Kojima, K., Linington, C., Wekerle, H., & Lassmann, H. (1997). Experimental autoimmune encephalomyelitis: The antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Laboratory Investigation, 76, 355–364.

    PubMed  CAS  Google Scholar 

  • Bergeron, M., Gidday, J. M., Yu, A. Y., Semenza, G. L., Ferriero, D. M., & Sharp, F. R. (2000). Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Annals of Neurology, 48, 285–296.

    PubMed  CAS  Google Scholar 

  • Bergsteindottir, K., Brennan, A., Jessen, K. R., & Mirsky, R. (1992). In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules. Proceedings of the National Academy of Sciences of the United States of America, 89, 9054–9058.

    PubMed  CAS  Google Scholar 

  • Bernaudin, M., Tang, Y., Reilly, M., Petit, E., & Sharp, F. R. (2002). Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. Journal of Biological Chemistry, 277, 39728–39738.

    PubMed  CAS  Google Scholar 

  • Brune, B., & Zhou, J. (2007). Hypoxia-inducible factor-1alpha under the control of nitric oxide. Methods in Enzymology, 435, 463–478.

    Article  PubMed  CAS  Google Scholar 

  • Buntinx, M., Gielen, E., Van Hummelen, P., Raus, J., Ameloot, M., Steels, P., et al. (2004). Cytokine-induced cell death in human oligodendroglial cell lines. II: Alterations in gene expression induced by interferon-gamma and tumor necrosis factor-alpha. Journal of Neuroscience Research, 76, 846–861.

    PubMed  CAS  Google Scholar 

  • Cannella, B., Gaupp, S., Omari, K. M., & Raine, C. S. (2007). Multiple sclerosis: Death receptor expression and oligodendrocyte apoptosis in established lesions. Journal of Neuroimmunology, 188, 128–137.

    PubMed  CAS  Google Scholar 

  • Cannella, B., Pitt, D., Capello, E., & Raine, C. S. (2000). Insulin-like growth factor-1 fails to enhance central nervous system myelin repair during autoimmune demyelination. American Journal of Pathology, 157, 933–943.

    PubMed  CAS  Google Scholar 

  • Cannella, B., & Raine, C. S. (2004). Multiple sclerosis: Cytokine receptors on oligodendrocytes predict innate regulation. Annals of Neurology, 55, 46–57.

    PubMed  CAS  Google Scholar 

  • Casaccia-Bonnefil, P., Gu, C., Khursigara, G., & Chao, M. V. (1999). p75 neurotrophin receptor as a modulator of survival and death decisions. Microscopy Research and Technique, 45, 217–224.

    PubMed  CAS  Google Scholar 

  • Chitnis, T., Najafian, N., Benou, C., Salama, A. D., Grusby, M. J., Sayegh, M. H., et al. (2001). Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. Journal of Clinical Investigation, 108, 739–747.

    PubMed  CAS  Google Scholar 

  • Christians, E. S., Yan, L. J., & Benjamin, I. J. (2002). Heat shock factor 1 and heat shock proteins: Critical partners in protection against acute cell injury. Critical Care Medicine, 30, S43–S50.

    CAS  Google Scholar 

  • Compston, A., McDonald, I., Noseworthy, J., Lassmann, H., Miller, D., Smith, K., et al. (2006). McAlpine’s multiple sclerosis. New York: Churchill Livingstone.

    Google Scholar 

  • Connor, J. R., & Menzies, S. L. (1995). Cellular management of iron in the brain. Journal of the Neurological Sciences, 134(Suppl), 33–44.

    PubMed  CAS  Google Scholar 

  • D’Souza, S. D., Alinauskas, K. A., & Antel, J. P. (1996). Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factor-mediated injury. Journal of Neuroscience Research, 43, 289–298.

    PubMed  CAS  Google Scholar 

  • D’Souza, S. D., & Antel, J. P. (1994). Freedman MS. Cytokine induction of heat shock protein expression in human oligodendrocytes: An interleukin-1-mediated mechanism. Journal of Neuroimmunology, 50, 17–24.

    PubMed  CAS  Google Scholar 

  • da Cunha, A., Jefferson, J. A., Jackson, R. W., & Vitkovic, L. (1993). Glial cell-specific mechanisms of TGF-beta 1 induction by IL-1 in cerebral cortex. Journal of Neuroimmunology, 42, 71–85.

    PubMed  Google Scholar 

  • De Groot, C. J., Ruuls, S. R., Theeuwes, J. W., Dijkstra, C. D., & Van der Valk, P. (1997). Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. Journal of Neuropathology and Experimental Neurology, 56, 10–20.

    PubMed  Google Scholar 

  • Du, Y., & Dreyfus, C. F. (2002). Oligodendrocytes as providers of growth factors. Journal of Neuroscience Research, 68, 647–654.

    PubMed  CAS  Google Scholar 

  • Freedman, M. S., Ruijs, T. C., Selin, L. K., & Antel, J. P. (1991). Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes. Annals of Neurology, 30, 794–800.

    PubMed  CAS  Google Scholar 

  • Genain, C. P., Cannella, B., Hauser, S. L., & Raine, C. S. (1999). Identification of autoantibodies associated with myelin damage in multiple sclerosis. Natural Medicines, 5, 170–175.

    CAS  Google Scholar 

  • Gibson, C. L., Coughlan, T. C., & Murphy, S. P. (2005). Glial nitric oxide and ischemia. Glia, 50, 417–426.

    PubMed  Google Scholar 

  • Gold, R., Hartung, H. P., & Toyka, K. V. (2000). Animal models for autoimmune demyelinating disorders of the nervous system. Molecular Medicine Today, 6, 88–91.

    PubMed  CAS  Google Scholar 

  • Gold, R., Linington, C., & Lassmann, H. (2006). Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain, 129, 1953–1971.

    PubMed  Google Scholar 

  • Graumann, U., Reynolds, R., Steck, A. J., & Schaeren-Wiemers, N. (2003). Molecular changes in normal appearing white matter in multiple sclerosis are characteristic of neuroprotective mechanisms against hypoxic insult. Brain Pathology, 13, 554–573.

    Article  PubMed  CAS  Google Scholar 

  • Grenier, Y., Ruijs, T. C., Robitaille, Y., Olivier, A., & Antel, J. P. (1989). Immunohistochemical studies of adult human glial cells. Journal of Neuroimmunology, 21, 103–115.

    PubMed  CAS  Google Scholar 

  • Greter, M., Heppner, F. L., Lemos, M. P., Odermatt, B. M., Goebels, N., Laufer, T., et al. (2005). Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Natural Medicines, 11, 328–334.

    CAS  Google Scholar 

  • Griot-Wenk, M., Griot, C., Pfister, H., & Vandevelde, M. (1991). Antibody-dependent cellular cytotoxicity in antimyelin antibody-induced oligodendrocyte damage in vitro. Journal of Neuroimmunology, 33, 145–155.

    PubMed  CAS  Google Scholar 

  • Gutcher, I., Urich, E., Wolter, K., Prinz, M., & Becher, B. (2006). Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation. Nature Immunology, 7, 946–953.

    PubMed  CAS  Google Scholar 

  • Gutteridge, J. M., & Halliwell, B. (1989). Iron toxicity and oxygen radicals. Baillieres Clinics in Haematology, 2, 195–256.

    CAS  Google Scholar 

  • Hill, K. E., Zollinger, L. V., Watt, H. E., Carlson, N. G., & Rose, J. W. (2004). Inducible nitric oxide synthase in chronic active multiple sclerosis plaques: Distribution, cellular expression and association with myelin damage. Journal of Neuroimmunology, 151, 171–179.

    PubMed  CAS  Google Scholar 

  • Hoftberger, R., Aboul-Enein, F., Brueck, W., Lucchinetti, C., Rodriguez, M., Schmidbauer, M., et al. (2004). Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions. Brain Pathology, 14, 43–50.

    Article  PubMed  CAS  Google Scholar 

  • Huseby, E. S., Liggitt, D., Brabb, T., Schnabel, B., Ohlen, C., & Goverman, J. (2001). A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. Journal of Experimental Medicine, 194, 669–676.

    PubMed  CAS  Google Scholar 

  • Iwakura, Y., & Ishigame, H. (2006). The IL-23/IL-17 axis in inflammation. Journal of Clinical Investigation, 116, 1218–1222.

    PubMed  CAS  Google Scholar 

  • Jack, C., Antel, J., Bruck, W., & Kuhlmann, T. (2007). Contrasting potential of nitric oxide and peroxynitrite to mediate oligodendrocyte injury in multiple sclerosis. Glia, 55, 926–934.

    PubMed  Google Scholar 

  • Jurewicz, A., Biddison, W. E., & Antel, J. P. (1998). MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes. Journal of Immunology, 160, 3056–3059.

    CAS  Google Scholar 

  • Jurewicz, A., Matysiak, M., Tybor, K., Kilianek, L., Raine, C. S., & Selmaj, K. (2005). Tumour necrosis factor-induced death of adult human oligodendrocytes is mediated by apoptosis inducing factor. Brain, 128, 2675–2688.

    PubMed  Google Scholar 

  • Juurlink, B. H., Thorburne, S. K., & Hertz, L. (1998). Peroxide-scavenging deficit underlies oligodendrocyte susceptibility to oxidative stress. Glia, 22, 371–378.

    PubMed  CAS  Google Scholar 

  • Kaplan, M. H., Schindler, U., Smiley, S. T., & Grusby, M. J. (1996). Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity, 4, 313–319.

    PubMed  CAS  Google Scholar 

  • Kennedy, P. G., & Steiner, I. (1994). On the possible viral aetiology of multiple sclerosis. QJM, 87, 523–528.

    PubMed  CAS  Google Scholar 

  • Kim, S. U. (1985). Antigen expression by glial cells grown in culture. Journal of Neuroimmunology, 8, 255–282.

    PubMed  CAS  Google Scholar 

  • Kreymborg, K., Etzensperger, R., Dumoutier, L., Haak, S., Rebollo, A., Buch, T., et al. (2007). IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis. Journal of Immunology, 179, 8098–8104.

    CAS  Google Scholar 

  • Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., et al. (2005). IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. Journal of Experimental Medicine, 201, 233–240.

    PubMed  CAS  Google Scholar 

  • Lassmann, H. (2003). Hypoxia-like tissue injury as a component of multiple sclerosis lesions. Journal of the Neurological Sciences, 206, 187–191.

    PubMed  CAS  Google Scholar 

  • Lassmann, H., & Ransohoff, R. M. (2004). The CD4-Th1 model for multiple sclerosis: A critical [correction of crucial] re-appraisal. Trends in Immunology, 25, 132–137.

    PubMed  CAS  Google Scholar 

  • Lee, S. C., & Raine, C. S. (1989). Multiple sclerosis: Oligodendrocytes in active lesions do not express class II major histocompatibility complex molecules. Journal of Neuroimmunology, 25, 261–266.

    PubMed  CAS  Google Scholar 

  • Li, J., Baud, O., Vartanian, T., Volpe, J. J., & Rosenberg, P. A. (2005). Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes. Proceedings of the National Academy of Sciences of the United States of America, 102, 9936–9941.

    PubMed  CAS  Google Scholar 

  • Li, H., Lebedeva, M. I., Llera, A. S., Fields, B. A., Brenner, M. B., & Mariuzza, R. A. (1998). Structure of the Vdelta domain of a human gammadelta T-cell antigen receptor. Nature, 391, 502–506.

    PubMed  CAS  Google Scholar 

  • Li, W., Maeda, Y., Ming, X., Cook, S., Chapin, J., Husar, W., et al. (2002). Apoptotic death following Fas activation in human oligodendrocyte hybrid cultures. Journal of Neuroscience Research, 69, 189–196.

    PubMed  CAS  Google Scholar 

  • Lin, W., Bailey, S. L., Ho, H., Harding, H. P., Ron, D., Miller, S. D., et al. (2007). The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage. Journal of Clinical Investigation, 117, 448–456.

    PubMed  CAS  Google Scholar 

  • Linington, C., Bradl, M., Lassmann, H., Brunner, C., & Vass, K. (1988). Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. American Journal of Pathology, 130, 443–454.

    PubMed  CAS  Google Scholar 

  • Liu, X., Yao, D. L., & Webster, H. (1995). Insulin-like growth factor I treatment reduces clinical deficits and lesion severity in acute demyelinating experimental autoimmune encephalomyelitis. Multiple Sclerosis, 1, 2–9.

    PubMed  CAS  Google Scholar 

  • Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H. (2000). Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Annals of Neurology, 47, 707–717.

    PubMed  CAS  Google Scholar 

  • Ludwin, S. K. (1997). The pathobiology of the oligodendrocyte. Journal of Neuropathology and Experimental Neurology, 56, 111–124.

    PubMed  CAS  Google Scholar 

  • Magliozzi, R., Howell, O., Vora, A., Serafini, B., Nicholas, R., Puopolo, M., et al. (2007). Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain, 130, 1089–1104.

    PubMed  Google Scholar 

  • McGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T., et al. (2007). TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nature Immunology, 8, 1390–1397.

    PubMed  CAS  Google Scholar 

  • McKinnon, R. D., Piras, G., Ida Jr., J. A., & Dubois-Dalcq, M. (1993). A role for TGF-beta in oligodendrocyte differentiation. Journal of Cell Biology, 121, 1397–1407.

    PubMed  CAS  Google Scholar 

  • Mead, R. J., Singhrao, S. K., Neal, J. W., Lassmann, H., & Morgan, B. P. (2002). The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. Journal of Immunology, 168, 458–465.

    CAS  Google Scholar 

  • Merrill, J. E., Ignarro, L. J., Sherman, M. P., Melinek, J., & Lane, T. E. (1993). Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. Journal of Immunology, 151, 2132–2141.

    CAS  Google Scholar 

  • Merrill, J. E., & Scolding, N. J. (1999). Mechanisms of damage to myelin and oligodendrocytes and their relevance to disease. Neuropathology & Applied Neurobiology, 25, 435–458.

    CAS  Google Scholar 

  • Micera, A., Properzi, F., Triaca, V., & Aloe, L. (2000). Nerve growth factor antibody exacerbates neuropathological signs of experimental allergic encephalomyelitis in adult lewis rats. Journal of Neuroimmunology, 104, 116–123.

    PubMed  CAS  Google Scholar 

  • Mitrovic, B., Ignarro, L. J., Vinters, H. V., Akers, M. A., Schmid, I., Uittenbogaart, C., et al. (1995). Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes. Neuroscience, 65, 531–539.

    PubMed  CAS  Google Scholar 

  • Nataf, S., Naveilhan, P., Sindji, L., Darcy, F., Brachet, P., & Montero-Menei, C. N. (1998). Low affinity NGF receptor expression in the central nervous system during experimental allergic encephalomyelitis. Journal of Neuroscience Research, 52, 83–92.

    PubMed  CAS  Google Scholar 

  • Newcombe, J., Uddin, A., Dove, R., Patel, B., Turski, L., Nishizawa, Y., et al. (2007). Glutamate receptor expression in multiple sclerosis lesions. Brain Pathology, 18(1), 52–61.

    PubMed  Google Scholar 

  • O’Connor, K. C., Appel, H., Bregoli, L., Call, M. E., Catz, I., Chan, J. A., et al. (2005). Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. Journal of Immunology, 175, 1974–1982.

    CAS  Google Scholar 

  • Oderfeld-Nowak, B., Zaremba, M., Lipkowski, A. W., Kwiatkowska-Patzer, B., Triaca, V., & Aloe, L. (2003). High-affinity NGF receptor in the rat spinal cord during acute and chronic phases of experimental autoimmune encephalomyelitis: A possible functional significance. Archives Italiennes de Biologie, 141, 103–116.

    PubMed  CAS  Google Scholar 

  • Oderfeld-Nowak, B., Zaremba, M., Micera, A., & Aloe, L. (2001). The upregulation of nerve growth factor receptors in reactive astrocytes of rat spinal cord during experimental autoimmune encephalomyelitis. Neuroscience Letters, 308, 165–168.

    PubMed  CAS  Google Scholar 

  • Odyniec, A., Szczepanik, M., Mycko, M. P., Stasiolek, M., Raine, C. S., & Selmaj, K. W. (2004). Gammadelta T cells enhance the expression of experimental autoimmune encephalomyelitis by promoting antigen presentation and IL-12 production. Journal of Immunology, 173, 682–694.

    CAS  Google Scholar 

  • Ozawa, K., Suchanek, G., Breitschopf, H., Bruck, W., Budka, H., Jellinger, K., et al. (1994). Patterns of oligodendroglia pathology in multiple sclerosis. Brain, 117(Pt 6), 1311–1322.

    PubMed  Google Scholar 

  • Parkin, J., & Cohen, B. (2001). An overview of the immune system. Lancet, 357, 1777–1789.

    PubMed  CAS  Google Scholar 

  • Pratt, B. M., & McPherson, J. M. (1997). TGF-beta in the central nervous system: Potential roles in ischemic injury and neurodegenerative diseases. Cytokine and Growth Factor Reviews, 8, 267–292.

    PubMed  CAS  Google Scholar 

  • Raine, C. S. (1997). The Norton lecture: A review of the oligodendrocyte in the multiple sclerosis lesion. Journal of Neuroimmunology, 77, 135–152.

    PubMed  CAS  Google Scholar 

  • Raine, C. S., Bonetti, B., & Cannella, B. (1998). Multiple sclerosis: Expression of molecules of the tumor necrosis factor ligand and receptor families in relationship to the demyelinated plaque. Revista de Neurología (Paris), 154, 577–585.

    CAS  Google Scholar 

  • Rajan, A. J., Gao, Y. L., Raine, C. S., & Brosnan, C. F. (1996). A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse. Journal of Immunology, 157, 941–949.

    CAS  Google Scholar 

  • Redford, E. J., Kapoor, R., & Smith, K. J. (1997). Nitric oxide donors reversibly block axonal conduction: Demyelinated axons are especially susceptible. Brain, 120(Pt 12), 2149–2157.

    PubMed  Google Scholar 

  • Redwine, J. M., Buchmeier, M. J., & Evans, C. F. (2001). In vivo expression of major histocompatibility complex molecules on oligodendrocytes and neurons during viral infection. American Journal of Pathology, 159, 1219–1224.

    PubMed  CAS  Google Scholar 

  • Reindl, M., Linington, C., Brehm, U., Egg, R., Dilitz, E., Deisenhammer, F., et al. (1999). Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: A comparative study. Brain, 122(Pt 11), 2047–2056.

    PubMed  Google Scholar 

  • Roskams, A. J., & Connor, J. R. (1994). Iron, transferrin, and ferritin in the rat brain during development and aging. Journal of Neurochemistry, 63, 709–716.

    PubMed  CAS  Google Scholar 

  • Ruijs, T. C., Freedman, M. S., Grenier, Y. G., Olivier, A., & Antel, J. P. (1990). Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes. Journal of Neuroimmunology, 27, 89–97.

    PubMed  CAS  Google Scholar 

  • Scolding, N. J., & Compston, D. A. (1991). Oligodendrocyte-macrophage interactions in vitro triggered by specific antibodies. Immunology, 72, 127–132.

    PubMed  CAS  Google Scholar 

  • Selmaj, K. W., & Raine, C. S. (1988). Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Annals of Neurology, 23, 339–346.

    PubMed  CAS  Google Scholar 

  • Semenza, G. (2002). Signal transduction to hypoxia-inducible factor 1. Biochemical Pharmacology, 64, 993–998.

    PubMed  CAS  Google Scholar 

  • Setzu, A., Lathia, J. D., Zhao, C., Wells, K., Rao, M. S., Ffrench-Constant, C., et al. (2006). Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells. Glia, 54, 297–303.

    PubMed  Google Scholar 

  • Sharp, F. R., Bergeron, M., & Bernaudin, M. (2001). Hypoxia-inducible factor in brain. Advances in Experimental Medicine and Biology, 502, 273–291.

    PubMed  CAS  Google Scholar 

  • Skulina, C., Schmidt, S., Dornmair, K., Babbe, H., Roers, A., Rajewsky, K., et al. (2004). Multiple sclerosis: Brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. Proceedings of the National Academy of Sciences of the United States of America, 101, 2428–2433.

    PubMed  CAS  Google Scholar 

  • Smith, K. J., Kapoor, R., & Felts, P. A. (1999). Demyelination: The role of reactive oxygen and nitrogen species. Brain Pathology, 9, 69–92.

    Article  PubMed  CAS  Google Scholar 

  • Smith, K. J., & Lassmann, H. (2002). The role of nitric oxide in multiple sclerosis. Lancet Neurology, 1, 232–241.

    PubMed  CAS  Google Scholar 

  • Sospedra, M., & Martin, R. (2005). Immunology of multiple sclerosis. Annual Review of Immunology, 23, 683–747.

    PubMed  CAS  Google Scholar 

  • Stadelmann, C., Ludwin, S., Tabira, T., Guseo, A., Lucchinetti, C. F., Leel-Ossy, L., et al. (2005). Tissue preconditioning may explain concentric lesions in Balo’s type of multiple sclerosis. Brain, 128, 979–987.

    PubMed  Google Scholar 

  • Stahnke, T., Stadelmann, C., Netzler, A., Bruck, W., & Richter-Landsberg, C. (2007). Differential upregulation of heme oxygenase-1 (HSP32) in glial cells after oxidative stress and in demyelinating disorders. Journal of Molecular Neuroscience, 32, 25–37.

    PubMed  CAS  Google Scholar 

  • Sun, D., Whitaker, J. N., Huang, Z., Liu, D., Coleclough, C., Wekerle, H., et al. (2001). Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. Journal of Immunology, 166, 7579–7587.

    CAS  Google Scholar 

  • Thorburne, S. K., & Juurlink, B. H. (1996). Low glutathione and high iron govern the susceptibility of oligodendroglial precursors to oxidative stress. Journal of Neurochemistry, 67, 1014–1022.

    Article  PubMed  CAS  Google Scholar 

  • van der Veen, R. C., & Roberts, L. J. (1999). Contrasting roles for nitric oxide and peroxynitrite in the peroxidation of myelin lipids. Journal of Neuroimmunology, 95, 1–7.

    PubMed  Google Scholar 

  • Villoslada, P., Hauser, S. L., Bartke, I., Unger, J., Heald, N., Rosenberg, D., et al. (2000). Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. Journal of Experimental Medicine, 191, 1799–1806.

    PubMed  CAS  Google Scholar 

  • Weaver, C. T., Harrington, L. E., Mangan, P. R., Gavrieli, M., & Murphy, K. M. (2006). Th17: An effector CD4 T cell lineage with regulatory T cell ties. Immunity, 24, 677–688.

    PubMed  CAS  Google Scholar 

  • Willenborg, D. O., Staykova, M. A., & Cowden, W. B. (1999). Our shifting understanding of the role of nitric oxide in autoimmune encephalomyelitis: A review. Journal of Neuroimmunology, 100, 21–35.

    PubMed  CAS  Google Scholar 

  • Williams, A., Piaton, G., & Lubetzki, C. (2007). Astrocytes—friends or foes in multiple sclerosis? Glia, 55, 1300–1312.

    PubMed  Google Scholar 

  • Wucherpfennig, K. W., Newcombe, J., Li, H., Keddy, C., Cuzner, M. L., & Hafler, D. A. (1992). Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proceedings of the National Academy of Sciences of the United States of America, 89, 4588–4592.

    PubMed  CAS  Google Scholar 

  • Ye, P., Kollias, G., D, , & Ercole, A. J. (2007). Insulin-like growth factor-I ameliorates demyelination induced by tumor necrosis factor-alpha in transgenic mice. Journal of Neuroscience Research, 85, 712–722.

    PubMed  CAS  Google Scholar 

  • Yoon, S. O., Casaccia-Bonnefil, P., Carter, B., & Chao, M. V. (1998). Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival. Journal of Neuroscience, 18, 3273–3281.

    PubMed  CAS  Google Scholar 

  • Zeis, T., Graumann, U., Reynolds, R., & Schaeren-Wiemers, N. (2008). Normal-appearing white matter in multiple sclerosis is in a subtle balance between inflammation and neuroprotection. Brain, 131, 288–303.

    PubMed  Google Scholar 

  • Zhang, J., Dawson, V. L., Dawson, T. M., & Snyder, S. H. (1994). Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science, 263, 687–689.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Prof. Dr. Burkhard Becher (Division of Neuroimmunology, University Hospital Zürich) and Dr. Anna Stalder (Neurobiology, Department of Biomedicine, University Hospital Basel) for the critical reading of the manuscript. This work was supported by the National Multiple Sclerosis Societies of Switzerland, France (ARSEP), United Kingdom, and United States of America.

Author information

Authors and Affiliations

  1. Neurobiology, Department of Biomedicine, University Hospital Basel, Pharmacenter 7007, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland

    T. Zeis & N. Schaeren-Wiemers

Authors
  1. T. Zeis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Schaeren-Wiemers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. Schaeren-Wiemers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zeis, T., Schaeren-Wiemers, N. Lame Ducks or Fierce Creatures? - The Role of Oligodendrocytes in Multiple Sclerosis. J Mol Neurosci 35, 91–100 (2008). https://doi.org/10.1007/s12031-008-9042-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-008-9042-1

Keywords

Search

Navigation