Advertisement

Brain Repair pp 99-112 | Cite as

Nerve Growth Factor (NGF) in the Central Nervous System: Implications for the Treatment of Alzheimer’s Disease

Chapter
  • 10 Downloads
Part of the Wenner-Gren Center International Symposium Series book series (WGS)

Abstract

The physiological functions of NGF in the peripheral nervous system are already known for a long time (see Levi-Montalcini and Angeletti, 1968; Greene and Shooter, 1980; Thoenen and Barde, 1980). NGF regulates the regionally differential survival of sympathetic and neural crest-derived sensory neurons. This regulatory function comes into play when the axons of NGF-responsive neurons reach their target area (see Davies et al., 1987; Barde, 1989). Furthermore, NGF is essential for the differentiation and maintenance of neuron-specific functions such as the synthesis of enzymes involved in the production of neurotransmitters and neuron-specific peptides e.g. substance P and somatostatin (see Thoenen and Barde, 1980; Otten 1984). NGF acts as a retrograde messenger transferring information from the fields of projection in the periphery to the innervating NGF-responsive neurons (see Davies et al., 1987; Barde 1989). Following Darwinian principles, NGF is produced in the target fields in very small quantities permitting the survival of a limited number of neurons only. ’Injection of exogenous NGF increases the survival of NGF responsive neurons, thus abolishing natural cell death which occurs during normal development (see Hendry, 1980; Thoenen and Barde, 1980).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Auburger, G., Heumann, R., Hellweg, R., Korsching, S., and Thoenen, H. (1987). Developmental changes of Nerve Growth Factor and its mRNA in the rat hippocampus: Comparison with choline acetyltransferase. Dev. Biol., 120, 322–328.PubMedCrossRefGoogle Scholar
  2. Ayer-LeLièvre, C., Olson, L., Ebendal, T., Seiger, Å., and Persson, H. (1988). Expression of the β-nerve growth factor gene in hippocampal neurons. Science, 240, 1339–1341.PubMedCrossRefGoogle Scholar
  3. Bandtlow, C.E., Heumann, R., Schwab, M.E., and Thoenen, H. (1987). Cellular localization of nerve growth factor synthesis by in situ hybridization. EMBO J., 6, 891–899.PubMedPubMedCentralGoogle Scholar
  4. Barde, Y.-A. (1989). Trophic factors and neuronal survival. Neuron, 2, 1525–1534.PubMedCrossRefGoogle Scholar
  5. Barth, E.-M., Korsching, S., and Thoenen, H. (1984). Regulation of Nerve Growth Factor synthesis and release in organ cultures of rat iris. J. Cell Biol., 99, 839–843.PubMedCrossRefGoogle Scholar
  6. Davies, A.M., Bandtlow, C., Heumann, R., Korsching, S., Rohrer, H., and Thoenen, H. (1987). The site and timing of nerve growth factor (NGF) synthesis in developing skin in relation to its innervation by sensory neurones and their expression of NGF receptors. Nature, 326, 353–363.PubMedCrossRefGoogle Scholar
  7. Dunnett, S.B., Low, W.C., Iversen, S.D., Stenevi, U. and Björklund A. (1982). Septal transplants restore maze learning in rats with fornix-fimbria lesions. Brain Res., 251, 335–348.PubMedCrossRefGoogle Scholar
  8. Ernfors, P., Hallböök, F., Ebendal, T., Shooter, E.M., Radeke, M.J., Misko, T.P., and Persson, H. (1988). β-nerve growth factor receptor mRNA in the chick and rat. Neuron, 1, 983–996.PubMedCrossRefGoogle Scholar
  9. Farrar, W.L., Hill, J.N., Harel-Bellan, A., and Vinocour, M. (1987a). The immune logical brain. Immunol. Rev., 199, 361–378.CrossRefGoogle Scholar
  10. Farrar, W.L., Kilian, P.L., Ruff, M.R., Hill, J.M., and Pert, C.B. (1987b). Visualization and characterization of interleukin-1 receptors in brain. J. Immunol., 139. 459–463.PubMedGoogle Scholar
  11. Fischer, W., Wictorin, K., Björklund, A., Williams, L.R., Varon, S., and Gage, F.H. (1987). Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature, 329, 65–68.PubMedCrossRefGoogle Scholar
  12. Fischer, W., Gage, F.H., and Björklund, A. (1989). Degenerative changes in forebrain cholinergic nuclei correlate with cognitive impairments in aged rats. Eur. J. Neurosci., 1, 34–45.PubMedCrossRefGoogle Scholar
  13. Furukawa, S., Furukawa, Y., Satoyoshi, E., and Hayashi, K. (1986). Synthesis and secretion of nerve growth factors by mouse astroglial cells in culture. Biochem. Biophys. Res. Commun., 136, 57–63.PubMedCrossRefGoogle Scholar
  14. Furukawa, S., Furukawa, Y., Satoyoshi, E., and Hayashi, K. (1987). Synthesis/secretion of nerve growth factor is associated with cell growth in cultured mouse astroglial cells. Biochem. Biophys. Res. Commun., 142, 395–402.PubMedCrossRefGoogle Scholar
  15. Gnahn, H., Hefti, F., Heumann, R., Schwab, M., and Thoenen, H. (1983). NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal forebrain: Evidence for a physiological role of NGF in the brain? Dev. Brain Res., 9, 45–52.CrossRefGoogle Scholar
  16. Goedert, M., Fine, A., Hunt, S.P., and Ullrich, A. (1986). Nerve growth factor mRNA in peripheral and central rat tissues and in the human central nervous system: Lesion effects in the rat brain and levels in Alzheimer’s disease. Mol. Brain Res., 1, 85–92.CrossRefGoogle Scholar
  17. Greene, L.A. and Shooter, E.M. (1980). The nerve growth factor: Biochemistry, synthesis, and mechanism of action. Ann. Rev. Neurosci., 3, 353–402.PubMedCrossRefGoogle Scholar
  18. Hazuda, D.J., Lee, J.C., and Young, P.R. (1988). The kinetics of interleukin 1 secretion from activated monocytes. J. Biol. Chem., 17, 8473–8479.Google Scholar
  19. Hefti, F. (1986). Nerve growth factor (NGF) promotes survival of septal cholinergic neurons after fimbrial transections. J. Neurosci., 6, 2155–2162.PubMedGoogle Scholar
  20. Hefti, F. and Weiner, W.J. (1986). Nerve growth factor and Alzheimer’s disease. Ann. Neurol., 20, 275–281.PubMedCrossRefGoogle Scholar
  21. Hendry, J.A. (1980). Proteins of the nervous system. 2nd ed. Bradshaw, R.A. and Schneier D.M. (eds.), Raven Press, New York, pp. 183–211.Google Scholar
  22. Heumann, R., Korsching, S., Bandtlow, C., and Thoenen, H. (1987a). Changes of nerve growth factor synthesis in non-neuronal cells in response to sciatic nerve transection. J. Cell Biol., 104, 1623–1631.PubMedCrossRefGoogle Scholar
  23. Heumann, R., Lindholm, D., Bandtlow, C., Meyer, M., Radeke, M.J., Misko, T.P., Shooter, E., and Thoenen, H. (1987b). Differential regulation of mRNa encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: Role of macrophages. Proc. Natl. Acad. Sci. USA, 84, 8735–8739.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Konkol, R.J., Mailman, R.B., Bendeich, E.G., Garrison, A.M., Mueller, R.A., and Breese, G.R. (1978). Evaluation of the effects of nerve growth factor and anti-nerve growth factor on the development of central catecholaminergic neurons. Brain Res., 144, 277–285.PubMedCrossRefGoogle Scholar
  25. Korsching, S., Auburger, G., Heumann, R., Scott, J., and Thoenen, H. (1985). Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J., 4, 1389–1393.PubMedPubMedCentralGoogle Scholar
  26. Large, T.H., Bodary, S.C., Clegg, D.O., Weskamp, G., Otten, U., and Reichardt, L.F. (1986). Nerve growth factor gene expression in the developing rat. Science, 234, 352–355.PubMedCrossRefGoogle Scholar
  27. Levi-Montalcini, R. and Angeletti, P.U. (1968). Nerve growth factor. Physiol. Rev., 48, 534–569.PubMedGoogle Scholar
  28. Lindholm, D., Heumann, R., Meyer, M., and Thoenen, H. (1987). Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve. Nature, 330, 658–659.PubMedCrossRefGoogle Scholar
  29. Lindholm, D., Heumann, R., Hengerer, B., and Thoenen, H. (1988). Interleukin 1 increases stability and transcription of mRNA encoding nerve growth factor in cultured rat fibroblasts. J. Biol. Chem., 263, 16348–16351.PubMedGoogle Scholar
  30. Lindsay, R.M. (1979). Adult rat brain astrocytes support survival of both NGF-dependent and NGF-insensitive neurons. Nature, 282, 80–82.PubMedCrossRefGoogle Scholar
  31. Mobley, W.C., Rutkowski, J.L., Tennekoon, G.I., Buchanan, K., and Johnston, M.V. (1985). Choline acetyltransferase in striatum of neonatal rats increased by nerve growth factor. Science, 229, 284–287.PubMedCrossRefGoogle Scholar
  32. Oppenheim, R.W., Maderdrut, J.L., and Wells, D.J. (1982). Cell death of motoneurons in the chick embryo spinal cord. VI. Reduction of naturally occurring cell death in the thoracolumbar column of Terni by nerve growth factor. J. comp. Neurol., 210, 174–189.PubMedGoogle Scholar
  33. Otten, U. (1984). Nerve growth factor and the peptidergic sensory neurons. Trends Pharmacol., 7, 307–310.CrossRefGoogle Scholar
  34. Raivich, G., Zimmermann, A., and Sutter, A. (1985). The spatial and temporal pattern of βNGF receptor expression in the developing chick embryo. EMBO J., 4, 637–644.PubMedPubMedCentralGoogle Scholar
  35. Raivich, G., and Kreutzberg, G.W. (1987). The localization and distribution of high affinity β-nerve growth factor binding sites in the central nervous system of the adult rat. A light microscopic autoradiographic study using [125I]β-nerve growth factor. Neuroscience, 20, 23–36.PubMedGoogle Scholar
  36. Rennert, P.D. and Heinrich, G. (1986). Nerve growth factor mRNA in brain: Localization by in situ hybridization. Biochem. Biophys. Res. Commun., 138, 813.PubMedCrossRefGoogle Scholar
  37. Richardson, P.M., Verge Issa, V.M.K., and Riopelle, R.J. (1986). Distribution of neuronal receptors for nerve growth factor in the rat. J. Neurosci., 6, 2312–2321.PubMedGoogle Scholar
  38. Schwab, M., Otten, U., Agid, Y., and Thoenen, H. (1979). Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra. Brain Res., 168, 473–483.PubMedCrossRefGoogle Scholar
  39. Seiler, M. and Schwab, M.E. (1984). Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Res., 300, 33–39.PubMedCrossRefGoogle Scholar
  40. Sofroniew, M.V., Isacson, O., and O’Brien, T.S. (1989). Nerve growth factor receptor immunoreactivity in the rat suprachiasmatic nucleus. Brain Res., 476, 358–362.PubMedCrossRefGoogle Scholar
  41. Springer J.E. and Loy, R. (1985). Intrahippocampal injections of antiserum to nerve growth factor inhibit sympathohippocampal sprouting. Brain Res. Bull., 15, 629–634.PubMedCrossRefGoogle Scholar
  42. Thoenen, H. and Barde, Y.-A. (1980). Physiology of nerve growth factor. Physiol. Rev., 60, 1284–1335.PubMedGoogle Scholar
  43. Thoenen, H., Bandtlow, C., and Heumann, R. (1987a). The physiological function of nerve growth factor in the central nervous system: Comparison with the periphery;. Rev. Physiol. Biochem. Pharmacol., 109, 145–178.PubMedGoogle Scholar
  44. Thoenen, H., Auburger, G., Hellweg, R., Heumann, R., and Korsching, S. (1987b). Cholinergic innervation and levels of nerve growth factor and its mRNA in the central nervous system. In Cholinergic Mechanisms. Ellis Horwood, Chichester, 379–388.Google Scholar
  45. Vantini, G., Fusco, M., Schiavo, N., Cavicchioli, L., Leon, A., and Toffano, G. (1988). In vivo effects of nerve growth factor (NGF) and anti-NGF antibodies on cholinergic neurons of rat basal forebrain. Senile dementia. II. Int. Symp., Agnoli, A., Conn, J., Lassen, N., and Mayeux, R. (eds.) John Libbey Eurotext, Paris, pp. 339–343.Google Scholar
  46. Whittemore, S.R., Ebendal, T., Lärkfors, L., Olson, L., Seiger, Å., Strömberg, I., and Persson, H. (1986). Developmental and regional expression of β nerve growth factor messenger RNA and protein in the rat central nervous system. Proc. Natl. Acad. Sci. USA. 83, 817–821.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Whittemore, S.R. and Seiger, Å. (1987). The expression localization and functional significance of beta-nerve growth factor in the central nervous system. Brain Res. Rev., 12, 439–464.CrossRefGoogle Scholar
  48. Whittemore, S.R., Friedman, P.L., Larhammar, D., Persson, H., Gonzales-Carvajal, M., and Holets, V.R. (1988). Rat β-nerve growth factor sequence and site of synthesis in the adult hippocampus. J. Neurosci. Res., 20, 403–410.PubMedCrossRefGoogle Scholar
  49. Yan, Q. and Johnson Jr., E.M. (1988). An immunohistochemical study of the nerve growth factor receptor in developing rats. J. Neurosci., 8, 3481–3498.PubMedGoogle Scholar
  50. Yan, Q., Snider, W.D., Pinzone, J.J., and Johnson Jr., E.M. (1988). Retrograde transport of Nerve Growth Factor (NGF) in motoneurons of developing rats: Assessment of potential neurotrophic effects. Neuron, 1, 335–343.PubMedCrossRefGoogle Scholar
  51. Yip, H.K. and Johnson, E.M. (1987). Nerve growth factor receptors in rat spinal cord: an autoradiographic and immunohistochemical study. Neuroscience, 22, 267–279.PubMedCrossRefGoogle Scholar

Copyright information

© The contributors 1990

Authors and Affiliations

  1. 1.Brain Research InstituteUniversity of ZürichSwitzerland

Personalised recommendations