Skip to main content
SpringerLink
Log in

Axonal pathology in myelin disorders

  • Published:
Journal of Neurocytology

Abstract

Myelination provides extrinsic trophic signals that influence normal maturation and long-term survival of axons. The extent of axonal involvement in diseases affecting myelin or myelin forming cells has traditionally been underestimated. There are, however, many examples of axon damage as a consequence of dysmyelinating or demyelinating disorders. More than a century ago, Charcot described the pathology of multiple sclerosis (MS) in terms of demyelination and relative sparing of axons. Recent reports demonstrate a strong correlation between inflammatory demyelination in MS lesions and axonal transection, indicating axonal loss at disease onset. Disruption of axons is also observed in experimental allergic encephalomyelitis and in Theiler's murine encephalomyelitis virus disease, two animal models of inflammatory demyelinating CNS disease. A number of dysmyelinating mouse mutants with axonal pathology have provided insights regarding cellular and molecular mechanisms of axon degeneration. For example, the myelin-associated glycoprotein and proteolipid protein have been shown to be essential for mediating myelin-derived trophic signals to axons. Patients with the inherited peripheral neuropathy Charcot-Marie Tooth disease type 1 develop symptomatic progressive axonal loss due to abnormal Schwann cell expression of peripheral myelin protein 22. The data summarized in this review indicate that axonal damage is an integral part of myelin disease, and that loss of axons contributes to the irreversible functional impairment observed in affected individuals. Early neuroprotection should be considered as an additional therapeutic option for these patients.

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

Similar content being viewed by others

References

  • Aguayo, A., Attiwell, M., Trecarten, J., Perkins, S. & Bray, G. (1977) Abnormal myelination in transplanted Trembler mouse Schwann cells. Na ture 265, 73–75.

    Google Scholar 

  • Anderson, T. J., Schneider, A., Barrie, J. A., Klugmann, M., Mcculloch, M. C., Kirkham, D., Kyriakides, E., Nave, K.-A. & Griffiths, I. R. (1998) Late-onset neurodegeneration in mice with increased dosage of the proteolipid protein gene. Journal of Comparative Neurology 394, 506–519.

    Google Scholar 

  • Anzini, P., Neuberg, D. D.-H., Schachner, M., Nelles, E., Willecke, K., Zielasek, J., Toyka, K. V., Suter, U. & Martini, R. (1997) Structural abnormalities and deficient maintenance of peripheral nerve myelin in mice lacking the gap junction protein connexin 32. Journal of Neuroscience 17, 4545–4551.

    Google Scholar 

  • Arnold, D. L., Reiss, G. T., Matthews, P. M., Francis, G. S., Collins, D. L., Wolfson, C. & Antel, J. P. (1994) Use of proton magnetic resonance spectroscopy for monitoring disease progression in multiple sclerosis. Annals of Neurology 36, 76–82.

    Google Scholar 

  • Arquint, M., Roder, J., Chia, L.-S., Down, J., Wilkinson, O., Bayley, H., Braun, P. & Dunn, R. (1987) Molecular cloning and primary structure of myelin-associated glycoproteins. Proceedings of the National Academy of Sciences (USA) 84, 600–604.

    Google Scholar 

  • Barnes, D., Munro, P. M. G., Youl, B. D., Prineas, J. W. & Mcdonald, W. I. (1991) The longstandingMS lesion. Brain 114, 1271–1280.

    Google Scholar 

  • Bell, J. I. & Lathrop, G. M. (1996) Multiple loci for multiple sclerosis. Nature Genetics 13, 377–378.

    Google Scholar 

  • Bergoffen, J., Scherer, S. S., Wang, S., Oronzi scott, M., Bone, L. J., Paul, D. L., Chen, K., Lensch, M. W., Chance, P. F. & Fischbeck, K. H. (1993) Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science 262, 2039–2042.

    Google Scholar 

  • Bjartmar, C., Rudick, R., MÖrk, S. & Trapp, B. D. (1999) Axonal transection in multiple sclerosis [abstract]. Journal of Neurochemistry 72, S40.

    Google Scholar 

  • Bradley, W. G. (1987) Recent viewsonamyotrophic lateral sclerosis with emphasis on electrophysiological studies. Muscle Nerve 10, 490–502.

    Google Scholar 

  • Brown, A., Mcfarlin, D. E. & Raine, C. S. (1982) Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. Laboratory Investigation 46, 171–185.

    Google Scholar 

  • BÖ, L., MÖrk, S., Kong, P. A., Nyland, H., Pardo, C. A. & Trapp, B. D. (1994) Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. Journal of Neuroimmunology 51, 135–146.

    Google Scholar 

  • Catterall, W. A. (1984) The molecular basis of neuronal excitability. Science 223, 653–661.

    Google Scholar 

  • Charcot, M. (1868) Histologie de le sclerose en plaques. Gazette Hopitaux 141, 554–558.

    Google Scholar 

  • Colello, R. J. & Pott, U. (1997) Signals that initiate myelination in the developing mammalian nervous system. Molecular Neurobiology 15, 83–100.

    Google Scholar 

  • Collins, B. E., Yang, L. J.-S., Mukhopadhyay, G., Filbin, M. T., Kiso, M., Hasegawa, A. & Schnaar, R. L. (1997) Sialic acid specificity of myelinassociated glycoprotein binding. Journal of Biological Chemistry 272, 1248–1255.

    Google Scholar 

  • Davie, C. A., Hawkins, C. P., Barker, G. J., Brennan, A., Tofts, P. S., Miller, D. H. & McDonald, W. I. (1994) Serial proton magnetic resonance spectroscopy in acute multiple sclerois lesions. Brain 117, 49–58.

    Google Scholar 

  • Davie, C. A., Barker, G. J., Webb, S., Tofts, P. S., Thompson, A. J., Harding, A. E., Mcdonald, W. I. & Miller, D. H. (1995) Persistent functional deficit in multiple sclerosis and autosomal dominant cerebellar ataxia is associated with axon loss. Brain 118, 1583–1592.

    Google Scholar 

  • De Stefano, N., Matthews, P. M., Antel, J. P., Preul, M., Francis, G. & Arnold, D. L. (1995) Chemical pathology of acute demyelinating lesions and its correlation with disability. Annals of Neurology 38, 901–909.

    Google Scholar 

  • De Stefano, N., Matthews, P. M., Fu, L., Narayanan, S., Stanley, J., Francis, G. S., Antel, J. P. & Arnold, D. L. (1998) Axonal damage correlates with disability in patients with relapsingremitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121, 1469–1477.

    Google Scholar 

  • De waegh, S. M. & Brady, S. T. (1990) Slow axonal transport in Trembler mouse: Altered cytoskeletal dynamics in a myelin deficient mouse model. Journal of Neuroscience 10, 1855–1865.

    Google Scholar 

  • De waegh, S. M. & Brady, S. T. (1991) Local control of axonal properties by Schwann cells: Neurofilaments and axonal transport in homologous and heterologous nerve grafts. Journal of Neuroscience Reserch 30, 201–212.

    Google Scholar 

  • De waegh, S. M., Lee, V. M.-Y. & Brady, S. T. (1992) Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells. Cell 68, 451–463.

    Google Scholar 

  • Dugandzija-novakovic, S., Koszowski, A. G., Levinson, S. R. & Shrager, P. (1995) Clustering of Na+ channels and node of Ranvier formation in remyelinating axons. Journal of Neuroscience 15, 492–503.

    Google Scholar 

  • Duncan, I. D., Hammang, J. P. & Trapp, B. D. (1988) Abnormal compact myelin in the myelin-deficient rat: Absence of proteolipid protein correlates with a defect in the intraperiod line. Proceedings of the National Academy of Sciences (USA) 84, 6287–6291.

    Google Scholar 

  • Drescher, K. M., Pease, L. R. & Rodriques, M. (1997) Antiviral immune responses modulate the nature of central nervous system (CNS) disease in a murine model of multiple sclerosis. Immunological Reviews 159, 177–193.

    Google Scholar 

  • Dyck, P. J., Karnes, J. L. & Lambert, E. H. (1989) Longitudinal study of neuropathic deficits and nerve conduction abnormalities in hereditary motor and sensory neuropathy type 1. Neurology 39, 1302–1308.

    Google Scholar 

  • Dyck, P. J., Chance, P., Lebo. R. & Carney, J. A. (1993) Hereditary motor and sensory neuropathies. In Peripheral neuropathy, 3rd ed. (edited by Dyck, P. J., Thomas, P. K., Griffin, J. W., Low, P. A. & Poduslo, J. F.), pp. 1094–1136. Philadelphia: WB Saunders.

    Google Scholar 

  • Ebers, G. C. & Dyment, D. A. (1998) Genetics of multiple sclerosis. Seminars in Neurology 18, 295–299.

    Google Scholar 

  • Ferguson, B., Matyszak, M. K., Esiri, M. M. & Perry, V. H. (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120, 393–399.

    Google Scholar 

  • Friedman, B., Scherer, S. S., Rudge, J. S., Helgren, M., Morrisey, D., Mcclain, J., Wang, D., Wiegand, S. J., Furth, M. E., Lindsay, R. M. & Ip, N. Y. (1992) Regulation of ciliary neurotrophic factor expression in myelin-related Schwann cells in vivo. Neuron 9, 295–305.

    Google Scholar 

  • Fu, L., Matthews, P. M., De stefano, N., Worsley, K. J., Narayanan, S., Francis, G. S., Antel, J. P., Wolfson, C. & Arnold, D. L. (1998) Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain 121, 103–113.

    Google Scholar 

  • Giese, K. P., Martini, R., Lemke, G., Soriano, P. & Schachner, M. (1992) Mouse P0 gene disruption leads to hypomyelination, abnormal expression of recognition molecules, and degeneration of myelin and axons. Cell 71, 565–576.

    Google Scholar 

  • Greenfield, J. G. & King, L. S. (1936) Observations on the histopathology of the cerebral lesions in disseminated sclerosis. Brain 59, 445–458.

    Google Scholar 

  • Griffiths, I. R., Schneider, A., Anderson, J. & Nave, K.-A. (1995) Transgenic and natural mouse models of proteolipid protein (PLP) related dysmyelination and demyelination. Brain Pathology 5, 275–281.

    Google Scholar 

  • Griffiths, I., Klugmann, M., Anderson, T., Yool, D., Thomson, C., Schwab, M. H., Schneider, A., Zimmermann, F., McCulloch, M., Nadon, N. & Nave, K.-A. (1998) Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280, 1610–1613.

    Google Scholar 

  • Hafer-macko, C., Hsieh, S.-T., Li, C. Y., Ho, T. W., Sheikh, K., Cornblath, D. R., Mckhann, G. M., Asbury, A. K. & Griffin, J. W. (1996) Acute motor axonal neuropathy: An antibody-mediated attack on axolemma. Annals of Neurology 40, 635–644.

    Google Scholar 

  • Hanemann, C. O. & MÖller, H. W. (1998) Pathogenesis of Charcot-Marie-Tooth IA (CMTIA) neuropathy. Trends in Neuroscience 21, 282–286.

    Google Scholar 

  • Hayasaka, K., Himoro, M., Sato, W., Takada, G., Uyemura, K., Shimizu, N., Bird, T. D., Coneally, P. M. & Chance, P. F. (1993) Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nature Genetics 5, 31–34.

    Google Scholar 

  • Helynck., G., Luu, B., Nussbaum, J. L., Picken, D., Skalidis, G., Trifilieff, E., Van dorsselaer, A., Seta, P., Sandeaux, R., Gavach, C., Heitz, F., Simon, D. & Spach, G. (1983) Brain proteolipids. Isolation, purification and effect on ionic permeability of membranes. European Journal of Biochemistry 133, 689–695.

    Google Scholar 

  • Hildebrand, C., Remahl, S., Persson, H. & Bjartmar, C. (1993) Myelinated nerve fibres in the CNS. Progress in Neurobiology 43, 85–141.

    Google Scholar 

  • Ho, T. W., Mckhann, G. M. & Griffin, J. W. (1998) Human autoimmune neuropathies. Annual Review of Neuroscience 21, 187–226.

    Google Scholar 

  • Hodes, M. E., Pratt, V. M. & Dlouhy, S. R. (1993) Genetics of Pelizaeus-Merzbacher disease. Developmental Neuroscience 15, 383–394.

    Google Scholar 

  • Hohlfeld, R. (1997) Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives [invited review]. BRAIN 120, 865–916.

    Google Scholar 

  • Inoue, K., Osaka, H., Imaizumi, K., Nezu, A., Takanashi, J., Arii, J., Murayama, K., Ono, J., Kikawa, Y., Mito, T., Shaffer, L. G. & Lupski, J. R. (1999) Proteolipid protein gene duplications causing Pelizaeus-Merzbacher disease: Molecular mechanism and phenotypic manifestations. Annals of Neurology 45, 624–632.

    Google Scholar 

  • Kaplan, M. R., Meyer-franke, A., Lambert, S., Bennett, V., Duncan, I. D., Levison, S. R. & Barres, B. A. (1997) Induction of sodium channel clustering by oligodendrocytes. Nature 386, 724–728.

    Google Scholar 

  • Kidd, D., Thorpe, J. W., Thompson, A. J., Kendall, B. E., Moseley, I. F., Macmanus, D. G., Mcdonald, W. I. & Miller, D. H. (1993) Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in multiple sclerosis. Neurology 43, 2632–2637.

    Google Scholar 

  • Kirkpatrick, L. L. & Brady, S. T. (1994) Modulation of the axonal microtubule cytoskeleton by myelinating Schwann cells. Journal of Neuroscience 14, 7440–7450.

    Google Scholar 

  • Kitagawa, K., Sinoway, M. P., Yang, C., Gould, R. M. & Colman, D. R. (1993) A proteolipid protein gene family: expression in sharks and rays and possible evolution from an ancestral gene encoding a poreforming polypeptide. Neuron 11, 433–448.

    Google Scholar 

  • Koo, E. H., Sisodia, S. S., Archer, D. R., Martin, L. J., Weidemann, A., Beyreuther, K., Fischer, P., Masters, C. L. & Price, D. L. (1990) Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proceedings of the National Academy of Sciences (USA) 87, 1561–1565.

    Google Scholar 

  • Lai, C., Brow, M. A., Nave, K.-A., Noronha, A. B., Quarles, R. H., Bloom, F. E., Milner, R. J. & Sutcliffe, J. G. (1987) Two forms of 1B236/myelinassociated glycoprotein (MAG), a cell adhesion molecule for postnatal neural development, are produced by alternative splicing. Proceedings of the National Academy of Sciences (USA) 84, 4337–4341.

    Google Scholar 

  • Li, C., Tropak, M. B., Gerial, R., Clapoff, S., Abramow-newerly, W., Trapp, B., Peterson, A. & Roder, J. (1994) Myelination in the absence of myelin-associated glycoprotein. Nature 369, 747–750.

    Google Scholar 

  • Li, M., Shibata, A., Li, C., Braun, P. E., McKerracher, L., Roder, J., Kater, S. B. & David, S. (1996) Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. Journal of Neuroscience Research 46, 404–414.

    Google Scholar 

  • Linington, C. (1998) Experimental animal models. In Immunotherapy in Neuroimmunologic Diseases, (edited by Zhang, J., Hafler, D., Hohlfeld, R. & Miller, A.), pp. 11–28. London: Martin Dunitz.

    Google Scholar 

  • Lloyd, K. G. (1977) CNS compensation to dopamine neuron loss in Parkinson's disease. Advances in Experimental Medicine and Biology 90, 255–266.

    Google Scholar 

  • Losseff, N. A., Webb, S. L., O'riordan, J. I., Page, R., Wang, L., Barker, G. J., Tofts, P. S., McDonald, W. I., Miller, D. H. & Thompson, A. J. (1996a) Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119, 701–708.

    Google Scholar 

  • Losseff, N. A., Wang, L., Lai, H. M., Yoo, D. S., Gawne-cain, M. L., Mcdonald, W. I., Miller, D. H. & Thompson, A. J. (1996b) Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 119, 2009–2019.

    Google Scholar 

  • Losseff, N. A. & Miller, D. H. (1998) Measures of brain and spinal cord atrophy in multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry 64, S102–S105.

    Google Scholar 

  • Low, P. A. & Mcleod, J. G. (1975) Hereditary demyelination neuropathy in the Trembler mouse. Journal of the Neurological Sciences 26, 565–574.

    Google Scholar 

  • Lublin, F. D. & Reingold, S. C. (1996) Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 46, 907–911.

    Google Scholar 

  • Matthews, P. M., Pioro, E., Narayanan, S., De Stefano, N., Fu, L., Francis, G., Antel, J., Wolfson, C. & Arnold, D. L. (1996) Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy. Brain 119, 715–722.

    Google Scholar 

  • Matthews, P. M., De stefano, N., Narayanan, S., Francis, G. S., Wolinsky, J. S., Antel, J. P. & Arnold, D. L. (1998) Putting magnetic resonance spectroscopy studies in context: Axonal damage and disability in multiple sclerosis. Seminars in Neurology 18, 327–336.

    Google Scholar 

  • Mcfarland, H. F., Frank, J. A., Albert, P. S., Smith, M. E., Martin, R., Harris, J. O., Patronas, N., Maloni, H. & Mcfarlin, D. E. (1992) Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis. Annals of Neurology 32, 758–766.

    Google Scholar 

  • Mckerracher, L., David, S., Jackson, D. L., Kottis, V., Dunn, R. J. & Braun, P. E. (1994) Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13, 805–811.

    Google Scholar 

  • Mews, I., Bergmann, M., Bunkowski, S., Gullotta, F. & BrÑck, W. (1998) Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions. Multiple Sclerosis 4, 55–62.

    Google Scholar 

  • Montag, D., Giese, K. P., Bartsch, U., Martini, R., Lang, Y., BlÑthmann, H., Karthigasan, J., Kirschner, D. A., Wintergerst, E. S., Nave, K.-A., Zielasek, J., Toyka, K. V., Lipp, H.-P. & Schachner, M. (1994) Mice deficient for the myelinassociated glycoprotein show subtle abnormalities in myelin. Neuron 13, 229–246.

    Google Scholar 

  • Mukhopadhyay, G., Doherty, P., Walsh, F. S., Crocker, P. R. & Filbin, M. T. (1994) A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13, 757–767.

    Google Scholar 

  • Narayanan, S., Fu, L., Pioro, E., De stefano, N., Collins, D. L., Francis, G. S., Antel, J. P., Matthews, P. M. & Arnold, D. L. (1997) Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions. Annals of Neurology 41, 385–391.

    Google Scholar 

  • Njenga, M. K., Murray, P. D., Mcgavern, D., Lin, X., Drescher, K. M. & Rodriguez, M. (1999) Absence of spontaneous central nervous system remyelination in class II-deficient mice infected with Theiler's virus. Journal of Neuropathology and Experimental Neurology 58, 78–91.

    Google Scholar 

  • Notterpek, L. M. & Rome, L. H. (1994) Functional evidence for the role of axolemma in CNS myelination. Neuron 13, 473–485.

    Google Scholar 

  • Oppenheimer, D. R. (1978) The cervical cord in multiple sclerosis. Neuropathology and Applied Neurobiology 4, 151–162.

    Google Scholar 

  • Owens, T. & Sriram, S. (1995) The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurologic Clinics 13, 51–73.

    Google Scholar 

  • Perkins, S., Aguayo, A. & Bray, G. (1981) Behaviour of Schwann cells from Trembler mouse unmyelinated fibers transplanted into myelinated nerves. Experimental Neurology 71, 515–526.

    Google Scholar 

  • Prineas, J. W. & Mcdonald, W. I. (1997) Demyelinating diseases. In Greenfield's Neuropathology, 6th ed. (edited by Graham, D. I. & Lantos, P. L.), pp. 813–881. International Society of Neuropathology.

  • Powell, H. C. & Myers, R. R. (1996) The axon in Guillain-Barr, syndrome: Immune target or innocent bystander? Annals of Neurology 39, 4–5.

    Google Scholar 

  • Putnam, T. J. (1936) Studies in multiple sclerosis. Archives of Neurology and Psychiatry 35, 1289–1308.

    Google Scholar 

  • Raine, C. S. (1984) Biology of disease. Analysis of autoimmune demyelination: its impact upon multiple sclerosis. Laboratory Investigation 50, 608–635.

    Google Scholar 

  • Raine, C. S. & Cross, A. H. (1989) Axonal dystrophy as a consequence of long-term demyelination. Laboratory Investigation 60, 714–725.

    Google Scholar 

  • Ritchie, J. M. (1984) Physiological basis of conduction in myelinated nerve fibers. In Myelin (edited by Morell, P.), pp. 117–146. New York: Plenum Press.

    Google Scholar 

  • Rivera-quinones, C., Mcgavern, D., Schmelzer, J. D., Hunter, S. F., Low, P. A. & Rodriguez, M. (1998) Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis. Nature Medicine 4, 187–193.

    Google Scholar 

  • Rodriguez, M., Olezak, E. & Leibowitz, J. (1987) Theiler'smurine encephalomyelitis:Amodel of demyelination and persistence of virus. Critical Reviews in Immunology 7, 325–365.

    Google Scholar 

  • Rosenbluth, J. (1988) Role of glial cells in the differentiation and function of myelinated axons. International Journal of Developmental Neuroscience 6, 3–24.

    Google Scholar 

  • Rudick, R., Cohen, J. A., Weinstock-guttman, B., Kinkel, R. P. & Ransohoff, R. M. (1997) Management of Multiple Sclerosis. New England Journal of Medicine 337, 1604–1611.

    Google Scholar 

  • Sahenk, Z. & Chen, L. (1998) Abnormalities in the axonal cytoskeleton induced by a Connexin32 mutation in nerve xenografts. Journal of Neuroscience Research 51, 174–184.

    Google Scholar 

  • Sahenk, Z., Chen, L. & Mendell, J. R. (1999) Effects of PMP22 duplication and deletions on the axonal cytoskeleton. Annals of Neurology 45, 16–24.

    Google Scholar 

  • Salzer, J. L., Holmes, W. P. & Colman, D. R. (1987) The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. Journal of Cell Biology 104, 957–965.

    Google Scholar 

  • Sanchez, I., Hassinger, L., Paskevich, P. A., Shine, H. D. & Nixon, R. A. (1996) Oligodendroglia regulate the regional expansion of axon caliber and local accumulation of neurofilaments during development independently of myelin formation. Journal of Neuroscience 16, 5095–5105.

    Google Scholar 

  • Scherer, S. (1999) Axonal pathology in demyelinating diseases. Annals of Neurology 45, 6–7.

    Google Scholar 

  • Scherer, S. S., Xu, Y. T., Nelles, E., Fischbeck, K. & Bone, L. J. (1998) Connexin32-null mice develop demyelinating peripheral neuropathy. Glia 24, 8–20.

    Google Scholar 

  • Seitelberger, F. (1995) Neuropathology and genetics of Pelizaeus-Merzbacher disease. Brain Pathology 5, 267–273.

    Google Scholar 

  • Sheikh, K. A., Sun, J., Kawai, H., Crawford, T. O., Proia, R. L., Griffin, J. W. & Schnaar, R. L. (1999) Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects. Proceedings of the National Academy of Sciences (USA) 96, 7532–7537.

    Google Scholar 

  • Sternberger, N. H., Quarles, R. H., Itoyama, Y. & Webster, H. D. (1979) Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin forming cells of developing rats. Proceedings of the National Academy of Sciences (USA) 76, 1510–1514.

    Google Scholar 

  • Tasaki, I. (1982) Physiology and Electrochemistry of Nerve Fibers. New York: Academic.

    Google Scholar 

  • Trapp, B. D., Andrews, S. B., Cootauco, C. & Quarles, R. H. (1989) The myelin-associated glycoprotein is enriched in multivesicular bodies and periaxonal membranes of actively myelinating oligodendrocytes. Journal of Cell Biology 109, 2417–2426.

    Google Scholar 

  • Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., MÖrk, S. & BÖ, L. (1998) Axonal transection in the lesions of multiple sclerosis. New England Journal of Medicine 338, 278–285.

    Google Scholar 

  • Trapp, B. D., Ransohoff, R. M., Fisher, E. & Rudick, R. (1999) Neurodegeneration in multiple sclerosis: relationship to neurological disability. The Neuroscientist 5, 48–57.

    Google Scholar 

  • Voyvodic, J. T. (1989) Target size regulates calibre and myelination of sympathetic axons. Nature 342, 430–433.

    Google Scholar 

  • Waxman, S. G. (1998) Demyelinating diseasesÑnew pathological insights, new therapeutic targets. New England Journal of Medicine 338, 223–225.

    Google Scholar 

  • Windenbank, A. J., Wood, P., Bunge, R. P. & Dyck, P. J. (1985) Myelination determines the caliber of dorsal root ganglion neurons in culture. Journal of Neuroscience 5, 1563–1569.

    Google Scholar 

  • Yang, L. J.-S., Zeller, C. B., Shaper, N. L., Kiso, M., Hasegawa, A., Shapiro, R. E. & Schnaar, R. L. (1996) Gangliosides are neuronal ligands for myelin-associated glycoprotein. Proceedings of the National Academy of Sciences (USA) 93, 814–818.

    Google Scholar 

  • Yin, X., Crawford, T. O., Griffin, J. W., Tu, P., Lee, V. M.-Y., Li, C., Roder, J. & Trapp, B. D. (1998) Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons. Journal of Neuroscience 18, 1953–1963.

    Google Scholar 

  • Yu, M., Nishiyama, A., Trapp, B. D., Tuohy, V. (1996) Interferon-β inhibits progression of relapsingremitting experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 64, 91–100.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH, 44195, USA

    Carl Bjartmar, Xinghua Yin & Bruce D. Trapp

Authors
  1. Carl Bjartmar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinghua Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce D. Trapp
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bjartmar, C., Yin, X. & Trapp, B.D. Axonal pathology in myelin disorders. J Neurocytol 28, 383–395 (1999). https://doi.org/10.1023/A:1007010205037

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007010205037

Keywords

Search

Navigation