Summary
Nerve growth factor receptor, expressed in Schwann cells during early development of the PNS, is rarely found in the normal mature PNS. Following nerve transection nerve growth factor receptor is re-expressed at high levels in the Schwann cells of the denervated nerve fibres. In this study we asked if demyelination caused by an immune-mediated process or by physical destruction of myelin is associated with expression of nerve growth factor receptor, and if so, what cells are positive. We examined spinal roots and sciatic nerves from rats with experimental autoimmune neuritis and sciatic nerves from rats with focal demyelination produced by local application of lysolecithin. Both in 1 μm serial cryosections and in immunostained teased nerve fibres we found that the Schwann cells that were associated with demyelinated internodes expressed nerve growth factor receptor. Immunoreactivity for nerve growth factor receptor appeared first in a perinuclear ring, probably corresponding to the Golgi complex. In completely demyelinated internodes the postmitotic Schwann cells ensheathing the axons expressed nerve growth factor receptor on their plasmalemmae. Neighbouring Schwann cells with intact myelin sheaths remained nerve growth factor receptor negative. In contrast, Schwann cells of neighbouring unmyelinated fibres expressed prominent nerve growth factor receptor immunoreactivity. These data further indicate that expression of nerve growth factor receptor by Schwann cells does not require axonal degeneration, but can be stimulated by some factor associated with acute demyelination.
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References
Bandtlow, C. E., Heumann, R., Schwab, M. E. &Thoenen, H. (1987) Cellular localization of nerve growth factor synthesis byin situ hybridization.EMBO Journal 6, 891–9.
Chandler, C. E., Parsons, L. M., Hosang, M. &Shooter, E. M. (1984) A monoclonal antibody modulates the interaction of nerve growth factor with PC 12 cells.Journal of Biological Chemistry 259, 6882–9.
Dijkstra, C. D., Dopp, E. A., Joling, P. &Kraal, G. (1985) The heterogeneity of mononuclear phagocytes in lyphoid organs: distinct macrophage subpopulations in the rat recognized by the monoclonal antibodies ED1, ED2, and ED3.Immunology 54, 589–699.
Distefano, P. S. &Johnson Jr., E. M. (1988) Nerve growth factor receptors on cultured rat Schwann cells.Journal of Neuroscience 8, 231–41.
Griffin, J. W., Drucker, N., Benzaquen, M., Fahnestock, K. E., Charnes, L. &Stocks, A. (1987) Schwann cell proliferation and migration during paranodal demyelination.Journal of Neurosdence 7, 682–99.
Griffin, J. W., Stocks, E. A., Fahnestock, K. E., Van Praagh, A. &Trapp, B. D. (1990a) Schwann cell proliferation following lysolecithin-induced demyelination.Journal of Neurocytology 19 367–84.
Griffin, J. W., Stoll, G., Li, C. Y., Tyor, W. R. &Cornblath, D. R. (1990b) Macrophage responses in inflammatory demyelinating polyneuropathies.Annals of Neurology 27 (suppl), S64-S68.
Hahn, A. F., Feasby, T. E., Steele, A., Lovgren, D. S. &Berry, J. (1988) Demyelination and axonal degeneration in Lewis rat experimental allergic neuritis depend on myelin dosage.Laboratory Investigation 59, 115–26.
Hall, S. M. &Gregson, N. A. (1971) Thein vivo and ultrastructural effects of the injection of lysophosphatidyl choline into myelinated peripheral nerve fibers of the adult mouse.Journal Cell Science 9, 769–89.
Hall, S. M. (1983) The response of the (myelinating) Schwann cell population to multiple episodes of demyelination.Journal of Neurocytology 12, 1–12.
Hartung, H. P., Schäfer, B., Heininger, K., Stoll, G. &Toyka, K. V. (1988) The role of macrophages and eicosanoids in the pathogenesis of experimental allergic neuritis. Serial clinical, electrophysiological, biochemical, and morphological observations.Brain 111, 1039–59.
Hartung, H. P., Stoll, G. &Toyka, K. V. (1992) Immune regulation in peripheral nerve. InPeripheral Neuropathies. 3rd edition, (edited byDyck, P. J., Thomas, P. K., Griffin, J. W., Low, P. &Poduslo, J.) 418–44, Saunders: Philadelphia.
Heumann, R. (1987a) Regulation of the synthesis of nerve growth factor.Journal of Experimental Biology 132, 133–50.
Heumann, R., Korsching, S., Bandtlow, C. &Thoenen, H. (1987b) Changes in nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection.Journal of Cell Biology 104, 1623–31.
Heumann, R., Lindholm, D., Bandtlow, C., Meyer, M., Radeke, M. J., Misko, T. P., Shooter, E. M. &Thoenen, H. (1987c) Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages.Proceedings of the National Academy of Sciences (USA) 84, 8735–9.
Lemke, G. &Chao, M. (1988) Axons regulate Schwann cell expression of the major myelin and NGF receptor genes.Development 102, 499–504.
Levi-Montalcini, R. &Angeletti, P. W. (1968) Nerve growth factor.Physiological Reviews 48, 534–64.
Lindholm, D., Heumann, R., Meyer, M. &Thoenen, H. (1987) Interleukin-1 regulates synthesis of nerve growth factor in non-neural cells of rat sciatic nerve.Nature 330, 658–9.
Lindholm, D., Heumann, R., Hengerer, B. &Thoenen, H. (1988) Interleukin-1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts.Journal of Biological Chemistry 263, 16348–51.
Lisak, R. P. &Bealmear, B. (1991) Antibodies to inter-leukin-1 inhibit cytokine-induced proliferation of neonatal rat Schwann cellin vitro.Journal of Neuroimmunology 31, 123–32.
Matsuoka, I., Meyer, M. &Thoenen, H. (1991) Cell-type-specific regulation of nerve growth factor (NGF) synthesis in non-neuronal cells: comparison of Schwann cells with other cell types.Journal of Neuroscience 11, 3165–77.
Misko, P. M., Radecke, M. J. &Shooter, E. M. (1987) Nerve growth factor in neuronal development and maintenance.Journal of Experimental Biology 132, 177–90.
Pellegrino, R. G. &Spencer, P. S. (1985) Schwann Cell mitosis in response to regenerating peripheral axonsin vivo.Brain Research 341, 16–25.
Raivich, G. &Kreutzberg, G. W. (1987) Expression of growth factor recectors in injured nervous tissue. I. Axotomy leads to a shift in the cellular distribution of specific B-nerve growth factor binding in the injured and regenerating PNS.Journal of Neurocytology 16, 689–700.
Sobue, G., Yasuda, T., Mitsuma, T., Ross, A. H. &Pleasure, D. (1988) Expression of nerve growth factor receptor in human peripheral neuropathies.Annals of Neurology 24, 64–72.
Stoll, G., Griffin, J. W., Li, C. Y. &Trapp, B. D. (1989a) Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation.Journal of Neurocytology 18, 671–83.
Stoll, G., Trapp, B. D. &Griffin, J. W. (1989b) Macrophage function during Wallerian degeneration of rat optic nerve: clearance of degenerating myelin and Ia expression.Journal of Neuroscience 9, 2327–35.
Stoll, G. &Hartung, H. P. (1992) The role of macrophages in degeneration and immune-mediated demyelination of the peripheral nervous system.Advances in Neuroimmunology 2, 163–79.
Taniuchi, M., Clark, H. B. &Johnson Jr, E. M. (1986) Induction of nerve growth factor receptors in Schwann cells after axotomy.Proceedings of the National Academy of Sciences (USA) 83, 4093–8.
Taniuchi, M., Clark, H. B., Schweitzer, J. B. &Johnson Jr, E. M. (1988) Expression of nerve growth factor receptor by Schwann cells of axomomized nerves: ultrastructural location suppression by axonal contact, and binding properties.Journal of Neuroscience 8, 664–81.
Toews, A. D., Griffiths, I. R., Kyriakides, E., Goodrum, J. F., Eckermann, C. E., Morell, P. &Thomson, C. E. (1992) Primary demyelination induced by exposure to tellurium alters Schwann cell gene expression: a model for intracellular targeting of NGF receptor.Journal of Neuroscience 12, 3676–87.
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Stoll, G., Li, C.Y., Trapp, B.D. et al. Expression of NGF-receptors during immune-mediated and lysolecithin-induced demyelination of the peripheral nervous system. J Neurocytol 22, 1022–1029 (1993). https://doi.org/10.1007/BF01235746
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DOI: https://doi.org/10.1007/BF01235746