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Histochemical characterization of sensory neurons with high-affinity receptors for nerve growth factor

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Journal of Neurocytology

Summary

Approximately one half of the neurons in the lumbar dorsal root ganglion of adult rats display high-affinity receptors for nerve growth factor (NGF). To ascertain which types of sensory neurons are potentially responsive to NGF, adjacent cryostat sections of rat dorsal root ganglia were processed either for NGF-receptor using radioautography or by one of four histochemical procedures. Histograms of the densities of neuronal labelling by radioiodinated NGF were examined for subpopulations of lumbar sensory neurons with thiamine monophosphatase enzyme activity or with immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, or somatostatin. Virtually all neurons with strong CGRP immunoreactivity had high-affinity NGF binding sites, although some neurons with faintly positive CGRP immunoreactivity lacked such NGF binding. A subpopulation of large neurons, approximately 5% of the total, had dense labelling by125I-NGF but were not stained by this immunohistochemical technique for CGRP. Of the three major populations of small neurons those with substance P immunoreactivity were consistently and heavily labelled by radioiodinated NGF whereas those with somatostatin immunoreactivity or thiamine monophosphatase activity were not specifically labelled by radioautography. For these primary sensory neurons in mature rats the genes for substance P and CGRP seem to be strongly expressed only in neurons capable of responding to NGF. On the other hand, neurons containing somatostatin and thiamine monophosphatase invariably lack high-affinity NGF receptors.

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References

  • Adams, J. C. (1981) Heavy metal intensification of DAB-0based HRP reaction product.Journal of Histochemistry and Cytochemistry 29, 775.

    Google Scholar 

  • Amara, S. G., Arriza, J. L., Leff, S. E., Swanson, L. W., Evans, R. M. &Rosenfeld, M. G. (1985) Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide.Science 229, 1094–7.

    Google Scholar 

  • Chalazonitis, A., Peterson, E. R. &Crain, S. M. (1987) Nerve growth factor regulates the action potential duration of mature sensory neurons.Proceedings of the National Academy of Science (USA) 84, 289–93.

    Google Scholar 

  • Chandeer, C. E., Parsons, E. M., Hosang, M. &Shooter, E. M. (1984) A monoclonal antibody modulates the interation of nerve growth factor with PC12 cells.Journal of Biological Chemistry 259, 6882–9.

    Google Scholar 

  • Cs1llik, B., Schwab, M. E. &Thoenen, H. (1985) Transganglionic regulation of central terminals of dorsal root ganglion cells by nerve growth factor (NGF).Brain Research 331, 11–5.

    Google Scholar 

  • Davies, A. M., Bandtlow, C., Heumann, R., Korsching, S., Rohrer, H. &Thoenen, H. (1987) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor.Nature 326, 353–8.

    Google Scholar 

  • Diamond, J., Coughlin, M., Macintyre, L., Holmes, M. &Visheau, B. (1987) Evidence that endogenous β nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats.Proceedings of the National Academy of Science (USA) 84, 6596–600.

    Google Scholar 

  • Dimberg, Y., Hedlund, K. -O. &Ebendal, T. (1987) Effects of nerve growth factor on sensory neurons in the chick embryo.International Journal of Developmental Neuroscience 5, 207–13.

    Google Scholar 

  • Dodd, J., Jahr, C. E., Hamilton, P. N., Heath, M. J. S., Matthew, W. D. &Jessell, T. M. (1983) Cytochemical and physiological properties of sensory and dorsal horn neurons that transmit cutaneous sensation.Cold Spring Harbor Symposium on Quantitative Biology 48, 685–95.

    Google Scholar 

  • Fitzgerald, M., Wall, P. D., Goedert, M. &Emson, P. C. (1985) Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section.Brain Research 332, 131–41.

    Google Scholar 

  • Goedert, M., Stoeckel, K. &Otten, U. (1981) Biological importance of the retrograde axonal transport of nerve growth factor in sensory neurons.Proceedings of the National Academy of Science (USA) 78, 5895–8.

    Google Scholar 

  • Goedert, M., Otten, U., Hunt, S. P., Bond, A., Chapman, D., Schlumpe, M. &Lichtensteiger, W. (1984) Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia.Proceedings of the National Academy of Science (USA) 81, 1580–4.

    Google Scholar 

  • Goedert, M. &Hunt, S. P. (1987) The cellular localization of preprotachykinin A messenger RNA in the bovine nervous system.Neuroscience 22, 983–92.

    Google Scholar 

  • Hamburger, V., Brunso-Bechtold, J. K. &Yip, J. W. (1981) Neuronal death in the spinal ganglia of the chick embryo and its reduction by nerve growth factor.journal of Neuroscience 1, 60–71.

    Google Scholar 

  • Hempstead, B. L., Schleifer, L. S. &Chao, M. V. (1989) Expression of functional nerve growth factor receptors after gene transfer.Science 243, 373–5.

    Google Scholar 

  • Hosang, M. &Shooter, E. M. (1985) Molecular characteristics of nerve growth factor receptors on PC12 cells.Journal of Biological Chemistry 260, 655–62.

    Google Scholar 

  • HÖkfelt, T., Elde, R., Johansson, O., Luft, R., Nilsson, G. &Arimura, A. (1976) Immunohistochemical evidence for separate populations of somatostatin-containing and substance P-containing primary afferent neurons in the rat.Neuroscience 1, 131–6.

    Google Scholar 

  • Johnson, D., Lanahan, A., Buck, C. R., Seghal, A., Morgan, C., Mercer, E., Bothwell, M. &Chao, M. (1986) Expression and structure of the human NGF receptor.Cell 47, 545–54.

    Google Scholar 

  • Ju, G., Hökfelt, T., Brodin, E., Fahrenkrug, J., Fischer, J. A., Frey, P., Elde, R. P. &Brown, J. C.(1987) Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells.Cell and Tissue Research 247, 417–31.

    Google Scholar 

  • Knyihár-Csillik, E., Bezzegh, A., Böti, S. &Csillik, B. (1986) Thiamine monophosphatase: a genuine marker for transganglionic regulation of primary sensory neurons.Journal of Histochemistry and Cytochemistry 34, 363–71.

    Google Scholar 

  • Lawson, S. N. (1979) The postnatal development of large light and small dark neurons in mouse dorsal root ganglia: a statistical analysis of cell numbers and size.Journal of Neurocytology 8, 275–94.

    Google Scholar 

  • Lawson, S. N., Harper, A. A., Harper, E. I., Garson, J. A. &Anderton, B. H. (1984) A monoclonal antibody against neurofilament protein specifically labels a subpopulation of rat sensory neurones.Journal of Comparative Neurology 228, 263–72.

    Google Scholar 

  • Le Douarin, N. M. (1980) The ontogeny of the neural crest in avian embryo chimaeras.Nature 286, 663–9.

    Google Scholar 

  • Lee, Y., Takami, K., Kawai, Y., Girgis, S., Hillyard, C. J., Macintyre, I., Emson, P. C. &Tohyama, M. (1985) Distribution of calcitonin gene-related peptide in the rat peripheral nervous system with reference to its coexistence with substance P.Neuroscience 15, 1227–37.

    Google Scholar 

  • Lindsay, R. M. (1988) Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons.Journal of Neuroscience 8, 2394–405.

    Google Scholar 

  • Lindsay, R. M. &Harmar, A. J. (1989) Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons.Nature 337, 362.

    Google Scholar 

  • Maclean, D. B., Lewis, S. F. &Wheeler, F. B. (1988) Substance P content in cultured neonatal rat vagal sensory neurons: the effect of nerve growth factor.Brain Research 457, 53–62.

    Google Scholar 

  • Mandelzys, A. &Cooper, E. (1988) NGF and nicotinic ACh receptor expression on rat nodose neurons in culture.Society of Neuroscience Abstracts 14, 517.

    Google Scholar 

  • Mulderry, P. K., Ghatei, M. A., Spokes, R. A., Jones, P. M., Pierson, A. M., Hamid, Q. A., Kanse, S., Amara, S. G., Burrin, J. M., Legon, S., Polak, J. M. &Bloom, S. R. (1988) Differential expression of α-CGRP and β-CGRP by primary sensory neurons and enteric autonomie neurons of the rat.Neuroscience 25, 195–205.

    Google Scholar 

  • Nagy, J. I. &Hunt, S. P. (1982) Fluoride-resistant acid phosphatase-containing neurones in dorsal root ganglia are separate from those containing substance P or somatostatin.Neuroscience 7, 89–97.

    Google Scholar 

  • Otten, U. &Lorez, H. P. (1983) Nerve growth factor increases substance P, cholecystokinin and vasoactive intestinal polypeptide immunoreactivities in primary sensory neurons of newborn rats.Neuroscience Letters 34, 153–8.

    Google Scholar 

  • Radeke, M. J., Misko, T. P., Hsu, C., Herzenberg, L. A. &Shooter, E. M. (1987) Gene transfer and molecular cloning of the rat nerve growth factor receptor.Nature 325, 593–7.

    Google Scholar 

  • Raivich, G., Zimmermann, A. &Sutter, A. (1987) Nerve growth factor receptor expression in chick cranial development.Journal of Comparative Neurology 256, 229–15.

    Google Scholar 

  • Rich, K. M., Luszczynski, J. R., Osborne, P. A. &Johnson, E. M. (1987) Nerve growth factor protects adult sensory neurons from cell death and atrophy caused by nerve injury.Journal of Neurocytology 16, 261–8.

    Google Scholar 

  • Richardson, P. M. &Ebendal, T. (1982) Nerve growth activities in rat peripheral nerve.Brain Research 246, 57–64.

    Google Scholar 

  • Richardson, P. M. &Riopelle, R. J. (1984) Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons.Journal of Neuroscience 4, 1683–9.

    Google Scholar 

  • Richardson, P. M., Verge, V. M. K. &Riopelle, R. J. (1989) Quantitative radioautography for NGF receptors. InNerve Growth Factors (edited byRush, R. A.), pp. 315–26. Chichester: John Wiley & Sons.

    Google Scholar 

  • Robertson, B. &Grant, G. (1989) Immunocytochemical evidence for the localization of the GM1 ganglioside in carbonic anhydrase-containing and RT 97-immunoreactive rat primary sensory neurons.Journal of Neurocytology 18, 77–86.

    Google Scholar 

  • Rohrer, H. &Barde, Y. -A. (1982) Presence and disappearance of nerve growth factor receptors on sensory neurons in culture.Development Biology 89, 309–15.

    Google Scholar 

  • Ross, M., Löfstrandh, S., Gorin, P. D., Johnson, E. M. &Schwartz, J. P. (1981) Use of an experimental autoimmune model to define nerve growth factor dependency of peripheral and central substance P-containing neurons in the rat.Journal of Neuroscience 1, 1304–11.

    Google Scholar 

  • Ross, A. H., Grob, P., Both Well, M., Elder, D. E., Ernst, C. S., Marano, N., Ghrist, B. F. D., Slemp, C. C., Herlyn, M., Atkinson, B. &Koprowski, H. (1984) Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies.Proceedings of the National Academy of Science (USA) 81, 6681–5.

    Google Scholar 

  • Schwartz, J. P., Pearson, J. &Johnson, E. M. (1982) Effect of exposure to anti-NGF on sensory neurons of adult rats and guinea pigs.Brain Research 244, 378–81.

    Google Scholar 

  • Shelton, D. L. &Reichardt, L. F. (1984) Expression of the β-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs.Proceedings of the National Academy of Science (USA) 81, 7951–5.

    Google Scholar 

  • Sutter, A., Riopelle, R. J., Harris-Warwick, R. M. &Shooter, E. M. (1979) Nerve growth factor receptors.Journal of Biological Chemistry 254, 5972–82.

    Google Scholar 

  • Verge, V. M. K., Riopelle, R. J. &Richardson, P. M. (1989) Nerve growth factor receptors on normal and injured sensory neurons.Journal of Neuroscience 9, 914–22.

    Google Scholar 

  • Wong, V., Barrett, C. P., Donati, E. J. &Guth, L. (1987) Distribution of carbonic anhydrase activity in neurons of the rat.Journal of Comparative Neurology 257, 122–9.

    Google Scholar 

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Verge, V.M.K., Richardson, P.M., Benoit, R. et al. Histochemical characterization of sensory neurons with high-affinity receptors for nerve growth factor. J Neurocytol 18, 583–591 (1989). https://doi.org/10.1007/BF01187079

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  • DOI: https://doi.org/10.1007/BF01187079

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