Growth Factors in the Basal Ganglia

  • James H. Fallon
Part of the Advances in Behavioral Biology book series (ABBI, volume 32)


The body of literature on growth factor effects in the brain and periphery is rapidly expanding. Until recently, most growth factor studies have pertained to the periphery and peripheral nervous system (see Golde et al, 1980; Johnson et al, 1986; Bradshaw & Rubin, 1980 for review). However, a number of growth factors have recently been identified within the CNS and have been shown to exert mitogenic and/or neuronotrophic effects (Thoenen & Edgar, 1985; Herschman, 1986). Of these, the best characterized is nerve growth factor (NGF), which has been shown to exhibit a heterogeneous distribution throughout brain (Ayer-Lelievre et al, 1983; Shelton & Reichardt, 1986; Whittemore et al, 1986; Scott et al, 1981). It is synthesized primarily, but not exclusively, in cortex and hippocampus (Shelton and Reichardt, 1986; Whittemore et al., 1986), and is retrogradely transported as a ligand-receptor complex from these regions to cholinergic nucleus basalis neurons (Seiler and Schwab, 1984). In both nucleus basalis and striatum, NGF has been shown to regulate the activity of the cholinergic synthetic enzyme, choline acetyltransferase (Martinez et al., 1985). Given these findings, it has been proposed that NGF acts as a neuronotrophic survival factor for cholinergic neurons within the CNS and that dysregulation of NGF may play a role in the etiology of Alzheimer’s and Huntington’s disease, which have been correlated with degeneration of cholinergic systems (Bartus et al., 1982; Marx, 1986).


Epidermal Growth Factor Nerve Growth Factor Specific Growth Factor Lateral Septum Epidermal Growth Factor Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Almazan, G., Honegger, Matthieu, J.M., and Guentert, B., 1985, Epidermal growth factor and bovine growth hormone stimulate differentiation and myelination of brain cell aggregates in culture. Developmental Brain Research, 21: 257–264.CrossRefGoogle Scholar
  2. Ayer-LeLievre, C.S., Ebendal, T., Olson, L. and Seiger, A. 1983, Localization of nerve growth factor-like immunoreactivity in rat nervous tissue, Med. Biol., 61: 296–304.PubMedGoogle Scholar
  3. Bartus, R.T., Dean, R.L., Beer, B. and Lippa, A.S., 1982, The cholinergic hypothesis of geriatric memory dysfunction, Science, 217: 408–414.PubMedCrossRefGoogle Scholar
  4. Bradshaw, R.A. and Rubin, J.S., 1980, Polypeptide growth factors: some structural and mechanistic considerations, J. Supramolec. Struct., 14: 183– 199.CrossRefGoogle Scholar
  5. Carpenter, G. and Cohen, S., 1979, Epidermal growth factor (EGF), Ann. Rev. Biochem., 48: 193–216.PubMedCrossRefGoogle Scholar
  6. Carpenter, G., 1984, Properties of the receptor for epidermal growth factor, Cell, 37: 357–358.PubMedCrossRefGoogle Scholar
  7. Cohen, S, 1962, Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal, J. Biol. Chem, 237: 1555–1562.PubMedGoogle Scholar
  8. Cohen, S., 1972, Epidermal growth factor, J. Invest. Dermatol., 59: 13–6.PubMedCrossRefGoogle Scholar
  9. Danielle, S., Frati, L., Fiore, C. and Santoni, G., 1979, The effect of the epidermal growth factor (EGF) on the corneal epithelium in humans, Albrecht v. Graefes Arch. Ophtholmol, 210: 159–165.CrossRefGoogle Scholar
  10. Doolittle, R.F., Feng, D.F., and Johnson, M.S., 1984 Computer-based characterization of epidermal growth factor precursor, Nature, 307: 558–560.PubMedCrossRefGoogle Scholar
  11. Fallon, J.H., Seroogy, K.B., Loughlin, S.E., Morrison, R.S., Bradshaw, R.A., Knauer, D.J. and Cunningham, D.D., 1984, Epidermal growth factor immunoreactive material in the central nervous system: location and development, Science, 224: 1107–1109.PubMedCrossRefGoogle Scholar
  12. Fallon, J.H., Code, R., Seroogy, K., Kornblum, H., Leslie, F., Twardzik, D. and Lee, D., 1986, Localization and development of growth factors in the CNS: TGF and EGF. Soc. Neur. Abs. 7.Google Scholar
  13. Fischer, G., 1984, Growth requirements of immature astrocytes in serum-free hormonally defined media, J. Neurosci. Res., 12: 543–552.PubMedCrossRefGoogle Scholar
  14. Golde, D.W., Herschman, H.R., Lusis, A.J. and Groopman, J.E., 1980, Growth factors, Annals. Int. Med., 92: 650–662.Google Scholar
  15. Haigler, H., 1983, Epidermal growth factor: Cellular binding consequences. In. Growth and Maturation Factors, Wiley, New York, 117–147.Google Scholar
  16. Herschman, H.R., Goodman, R., Chandler, C., Simpson, D., Cawley, D., Cole, R. and deVellis, J. 1983, Is epidermal growth factor a modulator of nervous system function?, Birth Defects Series, 19: 79–94.Google Scholar
  17. Hirata, Y., Uchibashi, M., Nakajima, H., Fujita, T. and Matsukura, S., 1982, Presence of human epidermal growth factor in human cerebrospinal fluid. J. Clin, End. Metab., 55: 1174–1177.CrossRefGoogle Scholar
  18. Ibbotson, K.J., Twardzik, D.R., D’Souza, S.M., Hargreaves, W.R., Todaro, C.J., and Mundy, G.R. 1985, Stimulation of bone resorption in vitro by synthetic transforming growth factor-alpha, Science, 228: 1007–1009.PubMedCrossRefGoogle Scholar
  19. Johnson, E.M., Rich, K.M. and Yip, H.K., 1986 TINS 9:1–14.Google Scholar
  20. Kasselberg, A.G., Orth, D.N., Gray, M.E. and Stahlman, M.T., 1985, Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues, J. Histochem. Cytochem., 33: 315–332.PubMedCrossRefGoogle Scholar
  21. Leutz, A. and Schacher, M., 1981, Epidermal growth factor stimulates DNA -synthesis of astrocytes in primary cerebellar cultures. Cell Tiss. Res., 220: 393–404.CrossRefGoogle Scholar
  22. Martinez, H.J., Dreyfus, C.F., Tonakait, G.M., and Black, I.B. 1985, Nerve growth factor promotoes cholinergic development in brain striatal cultures. Proc. Nat. Acad. Sci. 82: 7777–7781.PubMedCrossRefGoogle Scholar
  23. Marx, J.L., 1986, Nerve growth factor acts in brain. Science 232: 1341–1342.PubMedCrossRefGoogle Scholar
  24. Nanney, L.B., Stoschede, C.M., Magid, M., and King, L.E., 1986, Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages. J. Invest. Derm. 83: 385–393.CrossRefGoogle Scholar
  25. Probmeier, R. and Schachner, M., 1986, Epidermal growth factor is not detectable in developing and adult rodent brain by a sensitive double-site enzyme immunoassay. Neurosci. Lett. 63: 290–294.CrossRefGoogle Scholar
  26. Rall, L.B., Scott, J., Bell, G.I., Crawford, R.J., Penschow, J.D., Niall, H.D., Coghlan, J.P., 1985 Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues, Nature, 313: 228–231.PubMedCrossRefGoogle Scholar
  27. Savage, C.R., Hash, J.H. and Cohen, S., 1973 Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization, J. Biol. Chem. 274: 7609–7611.Google Scholar
  28. Savage, C.R., and Cohen, S., 1972, Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization, J. Biol. Chem., 274: 7609–7611.Google Scholar
  29. Scott, S.M., Tarris, R., Eveloth, D., Mansfield, H., Weischel, M.F. and Fisher, D.A., 1981, Bioasay detection of mouse nerve growth factor (mNGF) in the brain of adult mice, J. Neurosci. Res., 6: 653–658.PubMedCrossRefGoogle Scholar
  30. 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
  31. Shelton, D.L., and Reichardt, L.F., 1986, Studies on the expression of the Beta nerve growth factor (NGF) gene in the central nervous system: Level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. Proc. Nat. Acad. Sci., 83: 2714–2718.PubMedCrossRefGoogle Scholar
  32. Shreiber, A., Winkler, M. and Derynck, R., 1986, Transforming growth factor alpha — a more potent angiogenic mediator than epidermal growth factor. Science, 232: 1248–1253.Google Scholar
  33. Simpson, D., Morrison, R., deVellis, T. and Herschman, H., 1982, Epidermal growth factor binding and mitogenic activity on purified populations of cells from the central nervous system. J. Neurosci. Res., 8: 453–462.PubMedCrossRefGoogle Scholar
  34. Tam, J., Marquardt, H., Rosberger, D., Wong, T. and Todaro, G., 1984, Synthesis of biologically active rat transforming growth factor. Nature, 309: 376– 378.PubMedCrossRefGoogle Scholar
  35. Thoenen, H. and Edgar, D., 1985 Neurotrophic factors, Science, 229: 238–242.PubMedCrossRefGoogle Scholar
  36. Wharton, K.A., Johansen, K.M., Xu, T. and Aotravnis, S., 1985, Nucleotide sequence from the neurogenic locus. Notch implies a gene product that shares homology with proteins containing EGF-like reagents. Cell, 43: 567– 581.PubMedCrossRefGoogle Scholar
  37. Whittemore, S.R., Ebenda, T., Larkjors, L., Olson, L., Seiger, A., Stromberg, I. and Persson, H., 1986, Developmental and regional expression of beta nerve growth factor messenger RNA and protein in the central nervous system. Proc. Nat. Acad. Sci, 83: 817–821.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • James H. Fallon
    • 1
  1. 1.Department of Anatomy and NeurobiologyUniversity of California at IrvineIrvineUSA

Personalised recommendations