Summary
In animal experiments, nerve transection is followed by expression of nerve growth factor receptors (NGFR) on Schwann cells of both motor and sensory nerve fibres distally to the site of the lesion. To determine whether denervated Schwann cells in amyotrophic lateral sclerosis (ALS) similarly express NGFR, a study was made of post-mortem material of peripheral nerves and ventral roots from ALS cases and age-matched controls, using immunolabelling methods. Dorsal roots and spinal cords were also examined for the presence of NGFR. In all the ALS cases and controls, NGFR immunostaining was seen in the outer layer of vessel walls, perineurial sheaths, connective tissue surrounding fascicles in nerve roots and in the substantia gelatinosa of the spinal cord. In ALS, NGFR staining was also present in the Schwann cells of degenerated nerve fibres in mixed peripheral nerves, in ventral roots and, to a lesser extent, in dorsal roots. NGFR immunoreactivity was also seen in elongated cells extending from the perifascicular connective tissue into the nerve fascicles. It is concluded that denervated Schwann cells in ALS express NGFR and that NGFR immunostaining on Schwann cells may be used as an indicator of axonal degeneration. The NGFR labelling in the dorsal roots supports the notion that ALS is not a pure motor syndrome.
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References
Adams JC (1981) Heavy metal intensification of DAB-based HRP reaction products. J Histochem Cytochem 29: 775–780
Banerjee SP, Snyder SH, Cuatrecasas P, Green LA (1973) Binding of nerve growth factor in superior cervical ganglia. Proc Natl Acad Sci USA 70: 2519–2523
Bonduelle M (1975) Amyotrophic lateral sclerosis. Handb Clin Neurol 22: 281–338
Chesa PG, Rettig WJ, Thomson TM, Old LJ, Melamed MR, (1988) Immunohistochemical analysis of nerve growth factor receptor expression in normal and malignant human tissues. J Histochem Cytochem 36: 383–389
Dayan AD, Graveson GS, Illis LS, Robinson PK (1969) Schwann cell damage in motoneuron disease. Neurology 19: 242–246
Dyck PJ, Stevens JC, Mulder DW, Espinosa RE (1975) Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis: morphometry of deep and superficial peroneal nerves. Neurology 25: 781–787
Ernfors P, Henschen A, Olson L, Persson H (1989) Expression of nerve growth factor receptor mRNA is developmentally regulated and increased after axotomy in rat spinal cord motoneurons. Neuron 2: 1605–1613
Frazier WA, Boyd LF, Bradshaw RA (1974) Properties of specific binding of 125I-nerve growth factor to responsive peripheral neurons. J Biol Chem 249: 5513–5519
Greene LA, Shooter EM (1980) The nerve growth factor: biochemistry, synthesis, and mechanism of action. Annu Rev Neurosci 3: 353–402
Hanyu N, Oguchi K, Yanagisawa N, Tsukagoshi H (1982) Degeneration and regeneration of ventral root motor fibers in amyotrophic lateral sclerosis. Morphometric studies of cervical ventral roots. J Neurol Sci 55: 99–115
Hefti F, Hartikka J, Salvatierra A, Weiner WJ, Mash DC (1986) Localization of nerve growth factor receptors in cholinergic neurons of the human basal forebrain. Neurosci Lett 69: 37–41
Herrup K, Shooter EM (1973) Properties of the β-nerve growth factor receptor of avian dorsal root ganglia. Proc Natl Acad Sci USA 70: 3884–3888
Heumann R, Korsching S, Bandtlow C, Thoenen H (1987) Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol 104: 1623–1631
Hilderink PH, Veldman H, Jennekens FGI (1989) A simple method for immunostaining of axons in plastic embedded material. Proceedings of the 30th Dutch Federation meeting. Dutch Foundation Federation of Medical Scientific Societies, Maastricht. Abstr no 169
Johnson EM, Rich KM, Yip HK (1986) The role of NGF in sensory neurons in vivo. Trends Neurosci 9: 33–37
Johnson EM, Taniuchi M, DiStefano PS (1988) Expression and possible function of nerve growth factor receptors in Schwann cells. Trends Neurosci 11: 299–304
Johnson GD, Davidson RS, McNamee KC, Russell G, Goodwin D, Holborow EJ (1982) Fading of immunofluorescence during microscopy: a study of the phenomenon and its remedy. J Immunol Methods 55: 231–242
Kawamura Y, Dyck PJ, Masatake S, Okazaki H, Tateishi J, Doi H (1981) Morphometric comparison of the vulnerability of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 40: 667–675
Levi-Montalcini R (1987) The Nerve Growth Factor 35 years later. Science 237: 1154–1162
Levi-Montalcini R, Angeletti P (1968) Nerve growth factor. Physiol Rev 48: 534–569
Lindsay RM (1979) Adult rat brain astrocytes support survival of both NGF-dependent and NGF-insensitive neurones. Nature 282: 80–82
Ohnishi Y, Makifuchi T, Ikuta F (1980) Morphometric investigation of the myelinated fibers of the anterior spinal roots in amyotrophic lateral sclerosis and Shy-Drager syndrome. Clin Neurol 20: 809–815
Perry VH, Brown MC, Gordon S (1987) The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. J Exp Med 165: 1218–1223
Raivich G, Kreutzberg GW (1987) Expression of growth factor receptors in injured nervous tissue. I. Axotomy leads to ashift in the cellular distribution of specific β-nerve growth factor binding in the injured and regenerating PNS. J Neurocytol 16: 689–700
Raivich G, Zimmermann A, Sutter A (1985) The spatial and temporal pattern of βNGF receptor expression in the developing chick embryo. EMBO J 4: 637–644
Schatteman GC, Gibbs L, Lanahan AA, Claude P, Bothwell M (1988) Expression of NGF receptor in the developing and adult primate central nervous system. J Neurosci 8: 860–873
Snider WD, Johnson EM (1989) Neurotrophic molecules. Ann Neurol 26: 489–506
Sobue G, Matsuoka Y, Mukai E, Takayanagi T, Sobue I, Hashizume Y (1981) Spinal and cranial motor nerve roots in amyotrophic lateral sclerosis and X-linked recessive bulbolspinal muscular atrophy: morphometric and teased fiber study. Acta Neuropathol (Berl) 55: 227–235
Sobue G, Matsuoka Y, Mukai E, Takayanagi T, Sobue I (1981) Pathology of myelinated fibers in cervical and lumbar ventral spinal roots in amyotrophic lateral sclerosis. J Neurol Sci 50: 413–421
Taniuchi M, Clark HB, Johnson EM (1986) Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci USA 83: 4094–4098
Taniuchi M, Clark HB, Schweitzer JB, Johnson EM (1988) Expression of nerve growth factor receptors by Schwann cells of axotomized peripheral nerves: ultrastructural location, suppression by axonal contact, and binding properties. J Neurosci 8: 664–681
Telerman-Toppet N, Coërs C (1978) Motor innervation and fiber-type pattern in amyotrophic lateral sclerosis and in Charcot-Marie-Tooth disease. Muscle Nerve 1: 133–139
Thoenen H, Barde YA (1980) Physiology of nerve growth factor. Physiol Rev 60: 1284–1335
Wohlfart G, Swank PL (1941) Pathology of amyotrophic lateral sclerosis, fiber analysis of the ventral roots and pyramidal tracts of the spinal cord. Arch Neurol Psychiatry 46: 783–799
Wood SJ, Pritchard J, Sofroniew MV (1990) Re-expression of nerve growth factor receptor after axonal injury recapitulates a developmental event in motor neurons: differential regulation when regeneration is allowed or prevented. Eur J Neurosci 2: 650–657
Yan Q, Johnson EM (1988) An immunohistochemical study of the nerve growth factor receptor in developing rats. J Neurosci 8: 3481–3498
Yasuda T, Sobue G, Mokuno K, Kreider B, Pleasure D (1987) Cultured rat Schwann cells express low affinity receptors for nerve growth factor. Brain Res 436: 113–119
Yip HK, Johnson EM (1987) Nerve growth factor receptors in rat spinal cord: an autoradiographic and immunohistochemical study. Neuroscience 22: 267–279
Zimmermann A, Sutter A (1983) β-Nerve growth factor (βNGF) receptors on glial cells. Cell-cell interaction between neurones and Schwann cells in cultures of chick sensory ganglia. EMBO J 2: 879–885
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Supported by a grant from the Foundation for Research of ALS and Spinal Muscular Atrophy
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Kerkhoff, H., Jennekens, F.G.I., Troost, D. et al. Nerve growth factor receptor immunostaining in the spinal cord and peripheral nerves in amyotrophic lateral sclerosis. Acta Neuropathol 81, 649–656 (1991). https://doi.org/10.1007/BF00296375
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DOI: https://doi.org/10.1007/BF00296375