Summary
The distribution of the neural-specific growth associated protein B-50 (GAP-43), which persists in the mature spinal cord and dorsal root ganglia, has been studied by light and electron microscopic immunohistochemistry in the cat. Throughout the spinal cord, B-50 immunoreactivity was seen confined to the neuropil, whereas neuronal cell bodies were unreactive. The most conspicuous immunostaining was observed in the dorsal horn, where it gradually decreased from superficial laminae (I–II) toward more ventral laminae (III–V), and in the central portion of the intermediate gray (mainly lamina X). In these regions, the labelling was localized within unmyelinated, small diameter nerve fibres and axon terminals. In the rest of the intermediate zone (laminae VI–VIII), B-50 immunoreactivity was virtually absent. The intermediolateral nucleus in the thoracic and cranial lumbar cord showed a circumscribed intense B-50 immunoreactivity brought about by the labelling of many axon terminals on preganglionic sympathetic neurons. In motor nuclei of the ventral horn (lamina IX), low levels of B-50 immunoreactivity were present in a few axon terminals on dendritic and somal profiles of motoneurons. In dorsal root ganglia, B-50 immunoreactivity was mainly localized in the cell bodies of small and medium-sized sensory neurons. The selective distribution of persisting B-50 immunoreactivity in the mature cat throughout sensory, motor, and autonomie areas of the spinal cord and in dorsal root ganglia suggests that B-50-positive systems retain in adult life the capacity for structural and functional plasticity.
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Arvidsson, U., Risling, M., Cullheim, S., Dagerlind, A., Lindå, H., Shupliakov, O., Ulfhake, B. &Hökfelt, T. (1992) On the distribution of GAP-43 and its relation to serotonin in adult monkeys and cat spinal cord and lower brainstem.European Journal of Neuroscience 4, 777–84.
Averill, S., Curtis, R., Wilkin, G. P. &Priestley, J. V. (1992) Ultrastructural localization of GAP-43 immunoreactive terminals in the adult rat spinal cord.Journal of Physiology 446, 600P.
Benowitz, L. I. &Perrone-Bizzozero, N. I. (1991) The relationship of GAP-43 to the development and plasticity of synaptic connections.Annals of the New York Academy of Sciences 67, 58–73.
Benowitz, L. I., Perronne, N. I., Finklestein, F. E. &Bird, E. D. (1989) Localization of the growth-associated phosphoprotein GAP-43 (B-50, F1) in the human cerebral cortex.Journal of Neuroscience 9, 990–5.
Benowitz, L. I., Rodriguez, W. R. &Neve, R. L. (1990) The pattern of GAP-43 immunostaining changes in the rat hippocampal formation during reactive synaptogenesis.Molecular Brain Research 8, 17–23.
Burry, R. B., Lah, J. J. &Hayes, D. M. (1992) GAP-43 distribution is correlated with development of growth cones and presynaptic terminals.Journal of Neurocytology 21, 413–25.
Cadelli, D. S., Bandtlow, C. E. &Schwab, M. E. (1992) Oligodendrocyte- and myelin-associated inhibitors of neurite outgrowth: their involvement in the lack of CNS regeneration.Experimental Neurology 115, 189–92.
Coggeshall, R. E., Reynolds, M. L. &Woolf, C. J. (1991) Distribution of the growth-associated protein GAP-43 in central processes of axotomized primary afferents in the adult rat spinal cord; presence of growth cone-like structures.Neuroscience Letters 131, 37–41.
Dekker, L. V., De Graan, P. N. E., Oestreicher, A. B., Versteeg, D. H. G. &Gispen, W. H. (1989) Inhibition of noradrenaline release by antibodies to B-50 (GAP-43).Nature 342, 74–6.
De Graan, P. N. E., Van Hooff, C. O. M., Tilly, C., Obstreicher, A. B., Schotman, P. &Gispen, W. H. (1985) Phosphoprotein B-50 in nerve growth cones from fetal rat brain.Neuroscience Letters 61, 235–41.
Dela Monte, S. M., Federoff, H. J., Ng, S. C., Grabczyk, E., Fishman, M. C. (1989) GAP-43 gene expression during development: persistence in a distinctive set of neurons.Developmental Brain Research 46, 161–8.
Difiglia, M., Roberts, R. C. &Benowitz, L. I. (1990) Immunoreactive GAP43 in the neuropil of adult rat neostriatum: localization in unmyelinated fibres, axon terminals, and dendritic spines.Journal of Comparative Neurology 302, 992–1001.
Gispen, W. H., Nielander, H. B., De Graan, P. N. E., Oestreicher, A. B., Schrama, L. H. &Schotman, P. (1992) Role of the growth-associated protein B-50/GAP-43 in neuronal plasticity.Molecular Neurobiology 5, 61–85.
Goldberger, M. E. &Murray, M. (1988) Patterns of sprouting and implications for recovery of function.Advances in Neurology 47, 361–85.
Gordon-Weeks, P. R. (1989) GAP-43 — what does it do in the growth cone?Trends in Neuroscience 12, 363–5.
Gorgels, T. G. M. F., Oestreicher, A. B., De Kort, E. J. M. &Gispen, W. H. (1987) Immunocytochemical distribution of the protein kinase C substrate B-50 (GAP-43) in developing rat pyramidal tract.Neuroscience Letters 83, 59–64.
Gorgels, T. G. M. F., Van Lookeren Campagne, M., Oestreicher, A. B., Gribnau, A. A. M. &Gispen, W. H. (1989) B-50/GAP-43 is localized at the cytoplasmic side of the plasma membrane in developing and adult rat pyramidal tract.Journal of Neuroscience 9, 3861–9.
Goshgarian, H. G., Xioa-Jun, Y. &Rafols, J. A. (1989) Neuronal and glial changes in the rat phrenic nucleus occurring within hours after spinal cord injury.Journal of Comparative Neurology 284, 519–33.
Hulsebosch, C. E. &Goggeshall, R. E. (1981) Sprouting of dorsal root axons.Brain Research 224, 170–4.
Kalil, K. &Skene, J. H. P. (1986) Elevated synthesis of an axonally transported protein correlates with axon outgrowth in normal and injured pyramidal tracts.Journal of Neuroscience 6, 2563–70.
Knyihar-Csillik, E., Csillik, B. &Oestreicher, A. B. (1992) Light and electron microscopic localization of B-50 (GAP-43) in the rat spinal cord during transganglionic degenerative and regenerative atrophy and regeneration.Journal of Neuroscience Research 32, 93–109.
Lamotte, C. C., Kapadia, S. E. &Kokol, C. M. (1989) Deafferentation-induced expansion of saphenous terminal field labelling in the adult rat dorsal horn following pronase injection of the sciatic nerve.Journal of Comparative Neurology 288, 311–25.
Lieberman, A. R. (1976) Sensory ganglia. InThe Peripheral Nerve (edited byLandon, D. N.) pp. 188–278. London: Chapman and Hall.
Lovinger, D. M., Akers, R. M., Nelson, R. B., Barnes, C. A., McNaughton, B. L. &Routtenberg, A. (1985) A selective increase in the phosphorylation of protein F1, a protein kinase C substrate, directly related to three day growth of long term synaptic enhancement.Brain Research 343, 137–43.
Mahalik, T. J., Carrier, A., Owens, G. P., Clayton, G. (1992) The expression of GAP-43 mRNA during the late embryonic and early postnatal development of the CNS of the rat: an in situ hybridization study.Developmental Brain Research 67, 75–83.
Mashliah, E., Fagan, A. M., Terry, R. D., Deteresa, R. M., Malory, M. &Gage, F. (1991) Reactive synaptogenesis assessed by synaptophysin immunoreactivity is associated with GAP-43 in the dentate gyrus of the adult rat.Experimental Neurology 113, 131–42.
McIntosh, H., Parkinson, D., Meiri, K., Daw, N. &Willard, M. (1989) A GAP-43 like protein in cat visual cortex.Visual Neuroscience 2, 583–91.
McMahon, S. B. &Kett-White, R. (1991) Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system.Journal of Comparative Neurology 304, 307–15.
McNeill, D. L., Carlton, S. M. &Hulsebosch, C. E. (1991) Intraspinal sprouting of calcitonin gene-related petide containing primary afferents after deafferentation in the rat.Experimental Neurology 114, 321–9.
Meiri, K., Pfenninger, K. &Willard, M. (1986) Growth-associated protein, GAP-43, a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to a major polypeptide enriched in growth cones.Proceedings of the National Academy of Sciences (USA)83, 3537–41.
Mercken, M., Lübke, U., Vandermeeren, M., Gheuens, J. &Oestreicher, A. B. (1992) Immunocytochemical detection of the growth-associated protein B-50 by newly characterized monoclonal antibodies in human brain and muscle.Journal of Neurobiology 23, 309–21.
Nacimiento, W., Töpper, R., Fischer, A., Möbius, E., Oestreicher, A. B., Gispen, W. H., Nacimiento, A. C., Noth, J. &Kreutzberg, G. W. (1993) B-50 (GAP-43) in Onuf's nucleus of the adult cat.Brain Research, in press.
Nageotte, J. (1907) Étude sur la greffe des ganglions rachidiens; variations et tropismes du neurone sensitif.Anatomischer Anzeiger 31, 225–45.
Nelson, B. R., Friedman, D. P., O'Neill, J. B., Mishkin, M. &Routtenberg, A. (1987) Gradients of protein kinase C substrate phosphorylation in primate visual system peak in visual memory storage areas.Brain Research 416, 387–92.
Oestreicher, A. B. &Gispen, W. H. (1986) Comparison of the immunocytochemical distribution of the phosphoprotein B-50 in the cerebellum and hippocampus of the immature and adult rat brain.Brain Research 375, 267–79.
Oestreicher, A. B., Van Dongen, C. J., Zwiers, H. &Gispen, W. H. (1983) Affinity-purified anti-B-50 protein antibody: interference with the function of the phosphoprotein B-50 in synaptic plasma membranes.Journal of Neurochemistry 41, 331–40.
Pannese, E. (1981) The satellite cells of the sensory ganglia.Advances in Anatomy, Embryology and Cell Biology 65, 30–6.
Polistina, D. C., Murray, M. &Goldberger, M. E. (1990) Plasticity of dorsal root and descending serotoninergic projections after partial deafferentation of the adult rat spinal cord.Journal of Comparative Neurology 299, 349–63.
Reier, P. J., Stokes, B. T., Thompson, F. J. &Anderson, D. K. (1992) Fetal cell grafts into resection and contusion/resection injuries of the rat and cat spinal cord.Experimental Neurology 115, 177–88.
Rodin, B. E. &Kruger, L. (1984) Absence of intraspinal sprouting in dorsal root axons caudal to a partial spinal hermisection: a horseradish peroxidase transport study.Somatosensory Research 2, 171–91.
Rodin, B. E., Sampogna, S. L. &Kruger, Lo. (1983) An examination of intraspinal sprouting in dorsal root axons with the tracer horseradish peroxidase.Journal of Comparative Neurology 215, 187–98.
Schnell, L. &Schwab, M. E. (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors.Nature 343, 269–72.
Schreyer, D. J. &Skene, J. H. P. (1991) Fate of GAP-43 in ascending spinal axons of DRG neurons after peripheral nerve injury: Delayed accumulation and correlation with regenerative potential.Journal of Neuroscience 11, 3738–51.
Schwab, M. E. (1990) Myelin-associated inhibitors of neurite growth.Experimental Neurology 109, 2–5.
Skene, J. H. P. (1989) Axonal growth-associated proteins.Annual Reviews of Neuroscience 12, 127–56.
Skene, J. H. P. &Willard, F. M. (1981) Changes in the axonally transported proteins during axon regeneration in toad retinal ganglion cells.Journal of Cell Biology 89, 96–103.
Skene, J. H. P., Jacobson, D., Snipes, J., McGuire, C. B., Norden, J. J. &Freeman, J. A. (1986) A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes.Science 233, 263–8.
Sommervaille, T., Reynolds, M. L. &Woolf, C. J. (1991) Time dependent differences in the increase in GAP-43 in dorsal root ganglion cells after peripheral axotomy.Neuroscience 45, 213–20.
Sternberger, L. A. (1979)Immunohistochemistry, 2nd ed. New York: J. Wiley.
Stewart, H. J. S., Cowen, T., Curtis, R., Wilkin, G. P., Mirsky, R. &Jessen, K. R. (1992) GAP-43 immunoreactivity is widespread in autonomie and sensory neurons in the rat.Neuroscience 47, 673–84.
Tetzlaff, W., Zwiers, H., Lederis, K., Cassar, L. &Bisby, M. A. (1989) Axonal transport and localization of B-50/GAP-43-like immunoreactivity in regenerating sciatic and facial nerves of the rat.Journal of Neuroscience 9, 1303–13.
Van Der Zee, C. E. E. M., Nielander, H. B., Vos, J. P., Lopes Da Silva, S., Verhaagen, J., Oestreicher, A. B., Schrama, L. H., Schotman, P. &Gispen, W. H. (1989) Expression of growth-associated protein B-50 (GAP-43) in dorsal root ganglia and sciatic nerve during regenerative sprouting.Journal of Neuroscience 9, 3505–12.
Van Hooff, C. O. M., De Graan, P. N. E., Oestreicher, A. B. &Gispen, W. H. (1988) B50 phosphorylation and polyphosphoinositide metabolism in nerve growth cone membranes.Journal of Neuroscience 8, 1789–95.
Van Lookeren Campagne, M., Oestreicher, A. B., Van Bergen En Henegouwen, P. M. P. &Gispen, W. H. (1989) Ultrastructural immunocytochemical localization of B-50/GAP-43, a protein kinase C substrate, in isolated presynaptic nerve terminals and neuronal growth cones.Journal of Neurocytology 18, 479–89.
Van Lookeren Campagne, M., Oestreicher, A. B., Van Bergen En Henegouwen, P. M. P. &Gispen, W. H. (1990) Ultrastructural double localization of B-50/GAP43 and synaptophysin (p38) in neonatal and adult rat hippocampus.Journal of Neurocytology 19, 948–61.
Verhaagen, J., Van Hooff, C. O. M., Edwards, P. M., De Graan, P. N. E., Oestreicher, A. B., Schotman, P., Jennekens, F. G. I. &Gispen, W. H. (1986) The kinase C substrate protein B-50 and axonal regeneration.Brain Research 17, 737–41.
Woolf, C. J., Reynolds, M. L., Molander, C., O'Brien, C., Lindsay, R. M. &Benowitz, L. I. (1990) The growth-associated protein GAP-43 appears in the dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury.Neuroscience 34, 465–78.
Woolf, C. J., Shortland, P. &Coggeshall, R. E. (1992) Peripheral nerve injury triggers central sprouting of myelinated afferents.Nature 355, 75–7.
Yasunobu, I. &Tessler, A. (1990) Ultrastructural organization of regenerated adult dorsal root axons within transplants of fetal spinal cord.Journal of Comparative Neurology 292, 396–411.
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Nacimiento, W., Töpper, R., Fischer, A. et al. Immunocytochemistry of B-50 (GAP-43) in the spinal cord and in dorsal root ganglia of the adult cat. J Neurocytol 22, 413–424 (1993). https://doi.org/10.1007/BF01181562
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DOI: https://doi.org/10.1007/BF01181562