Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Aug;84(15):5459–5463. doi: 10.1073/pnas.84.15.5459

Astroglial and fibroblast growth factors have neurotrophic functions for cultured peripheral and central nervous system neurons.

K Unsicker, H Reichert-Preibsch, R Schmidt, B Pettmann, G Labourdette, M Sensenbrenner
PMCID: PMC298877  PMID: 3474662

Abstract

Embryonic and neonatal neurons require specific trophic supplements for their survival and the induction of transmitter-synthesizing enzymes in vivo and in vitro. Acidic and basic fibroblast growth factor (aFGF, bFGF) and the closely related astroglial growth factors AGF-1 and AGF-2 were studied for putative neurotrophic functions using dissociated, highly neuron-enriched cultures from chick and rat peripheral ganglia and central nervous system tissues. Embryonic chick ciliary ganglion neurons were the only peripheral neurons that responded to bFGF and AGF-2 by enhanced survival equivalent to that obtained with ciliary neurotrophic factor. Half-maximal effects were achieved with bFGF at 360 pg/ml or AGF-2 at 3 ng/ml. Small effects seen with aFGF could be potentiated by adding heparin at 1 microgram/ml. bFGF, but not ciliary neurotropic factor, also promoted neuron survival after the factor was bound to polyornithine and laminin. Both AGF-2 and ciliary neurotropic factor induced choline acetyltransferase activity during 48 hr. AGFs and FGFs also enhanced the long-term survival of embryonic chick spinal cord neurons, including motoneurons that had been retrogradely labeled with rhodamine isothiocyanate. These results demonstrate the potency of a class of mitogenic growth factors as neurotrophic agents for embryonic ciliary ganglion and spinal cord neurons--adding to the emerging evidence that mitogenic and neuronal growth factors are not strictly separate entities.

Full text

PDF
5461

Images in this article

5460Image
on p.5460
5462Image
on p.5462

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baird A., Esch F., Böhlen P., Ling N., Gospodarowicz D. Isolation and partial characterization of an endothelial cell growth factor from the bovine kidney: homology with basic fibroblast growth factor. Regul Pept. 1985 Nov 7;12(3):201–213. doi: 10.1016/0167-0115(85)90061-8. [DOI] [PubMed] [Google Scholar]
  2. Baird A., Esch F., Gospodarowicz D., Guillemin R. Retina- and eye-derived endothelial cell growth factors: partial molecular characterization and identity with acidic and basic fibroblast growth factors. Biochemistry. 1985 Dec 31;24(27):7855–7860. doi: 10.1021/bi00348a001. [DOI] [PubMed] [Google Scholar]
  3. Barbin G., Manthorpe M., Varon S. Purification of the chick eye ciliary neuronotrophic factor. J Neurochem. 1984 Nov;43(5):1468–1478. doi: 10.1111/j.1471-4159.1984.tb05410.x. [DOI] [PubMed] [Google Scholar]
  4. Barbin G., Selak I., Manthorpe M., Varon S. Use of central neuronal cultures for the detection of neuronotrophic agents. Neuroscience. 1984 May;12(1):33–43. doi: 10.1016/0306-4522(84)90135-0. [DOI] [PubMed] [Google Scholar]
  5. Boonstra J., Moolenaar W. H., Harrison P. H., Moed P., van der Saag P. T., de Laat S. W. Ionic responses and growth stimulation induced by nerve growth factor and epidermal growth factor in rat pheochromocytoma (PC12) cells. J Cell Biol. 1983 Jul;97(1):92–98. doi: 10.1083/jcb.97.1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bottenstein J. E., Skaper S. D., Varon S. S., Sato G. H. Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. Exp Cell Res. 1980 Jan;125(1):183–190. doi: 10.1016/0014-4827(80)90202-5. [DOI] [PubMed] [Google Scholar]
  7. Böhlen P., Baird A., Esch F., Ling N., Gospodarowicz D. Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5364–5368. doi: 10.1073/pnas.81.17.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carnow T. B., Manthorpe M., Davis G. E., Varon S. Localized survival of ciliary ganglionic neurons identifies neuronotrophic factor bands on nitrocellulose blots. J Neurosci. 1985 Aug;5(8):1965–1971. doi: 10.1523/JNEUROSCI.05-08-01965.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Courty J., Chevallier B., Moenner M., Loret C., Lagente O., Bohlen P., Courtois Y., Barritault D. Evidence for FGF-like growth factor in adult bovine retina: analogies with EDGF I. Biochem Biophys Res Commun. 1986 Apr 14;136(1):102–108. doi: 10.1016/0006-291x(86)90882-x. [DOI] [PubMed] [Google Scholar]
  10. Courty J., Loret C., Moenner M., Chevallier B., Lagente O., Courtois Y., Barritault D. Bovine retina contains three growth factor activities with different affinity to heparin: eye derived growth factor I, II, III. Biochimie. 1985 Feb;67(2):265–269. doi: 10.1016/s0300-9084(85)80056-0. [DOI] [PubMed] [Google Scholar]
  11. Eccleston P. A., Silberberg D. H. Fibroblast growth factor is a mitogen for oligodendrocytes in vitro. Brain Res. 1985 Aug;353(2):315–318. doi: 10.1016/0165-3806(85)90221-4. [DOI] [PubMed] [Google Scholar]
  12. Fonnum F. A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem. 1975 Feb;24(2):407–409. doi: 10.1111/j.1471-4159.1975.tb11895.x. [DOI] [PubMed] [Google Scholar]
  13. Gospodarowicz D., Cheng J., Lui G. M., Baird A., Böhlent P. Isolation of brain fibroblast growth factor by heparin-Sepharose affinity chromatography: identity with pituitary fibroblast growth factor. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6963–6967. doi: 10.1073/pnas.81.22.6963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gospodarowicz D., Lepine J., Massoglia S., Wood I. Comparison of the ability of basement membranes produced by corneal endothelial and mouse-derived Endodermal PF-HR-9 cells to support the proliferation and differentiation of bovine kidney tubule epithelial cells in vitro. J Cell Biol. 1984 Sep;99(3):947–961. doi: 10.1083/jcb.99.3.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gospodarowicz D., Neufeld G., Schweigerer L. Molecular and biological characterization of fibroblast growth factor, an angiogenic factor which also controls the proliferation and differentiation of mesoderm and neuroectoderm derived cells. Cell Differ. 1986 Jul;19(1):1–17. doi: 10.1016/0045-6039(86)90021-7. [DOI] [PubMed] [Google Scholar]
  16. Hamburger V. Cell death in the development of the lateral motor column of the chick embryo. J Comp Neurol. 1975 Apr 15;160(4):535–546. doi: 10.1002/cne.901600408. [DOI] [PubMed] [Google Scholar]
  17. Lietzke R., Unsicker K. Tetanus toxin binding to different morphological phenotypes of cultured rat and bovine adrenal medullary cells. Neurosci Lett. 1983 Aug 8;38(3):233–238. doi: 10.1016/0304-3940(83)90374-9. [DOI] [PubMed] [Google Scholar]
  18. Lillien L. E., Claude P. Nerve growth factor is a mitogen for cultured chromaffin cells. Nature. 1985 Oct 17;317(6038):632–634. doi: 10.1038/317632a0. [DOI] [PubMed] [Google Scholar]
  19. Longo F. M., Manthorpe M., Varon S. Spinal cord neuronotrophic factors (SCNTFs): I. Bioassay of schwannoma and other conditioned media. Brain Res. 1982 Feb;255(2):277–294. doi: 10.1016/0165-3806(82)90027-x. [DOI] [PubMed] [Google Scholar]
  20. Manthorpe M., Engvall E., Ruoslahti E., Longo F. M., Davis G. E., Varon S. Laminin promotes neuritic regeneration from cultured peripheral and central neurons. J Cell Biol. 1983 Dec;97(6):1882–1890. doi: 10.1083/jcb.97.6.1882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morrison R. S., Sharma A., de Vellis J., Bradshaw R. A. Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7537–7541. doi: 10.1073/pnas.83.19.7537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Neufeld G., Gospodarowicz D. The identification and partial characterization of the fibroblast growth factor receptor of baby hamster kidney cells. J Biol Chem. 1985 Nov 5;260(25):13860–13868. [PubMed] [Google Scholar]
  23. Pettmann B., Labourdette G., Weibel M., Sensenbrenner M. The brain fibroblast growth factor (FGF) is localized in neurons. Neurosci Lett. 1986 Jul 24;68(2):175–180. doi: 10.1016/0304-3940(86)90137-0. [DOI] [PubMed] [Google Scholar]
  24. Pettmann B., Weibel M., Sensenbrenner M., Labourdette G. Purification of two astroglial growth factors from bovine brain. FEBS Lett. 1985 Sep 9;189(1):102–108. doi: 10.1016/0014-5793(85)80851-6. [DOI] [PubMed] [Google Scholar]
  25. Saneto R. P., de Vellis J. Effect of mitogens in various organs and cell culture conditioned media on rat oligodendrocytes. Dev Neurosci. 1985;7(5-6):340–350. doi: 10.1159/000112301. [DOI] [PubMed] [Google Scholar]
  26. Shing Y., Folkman J., Sullivan R., Butterfield C., Murray J., Klagsbrun M. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science. 1984 Mar 23;223(4642):1296–1299. doi: 10.1126/science.6199844. [DOI] [PubMed] [Google Scholar]
  27. Thomas K. A., Rios-Candelore M., Fitzpatrick S. Purification and characterization of acidic fibroblast growth factor from bovine brain. Proc Natl Acad Sci U S A. 1984 Jan;81(2):357–361. doi: 10.1073/pnas.81.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Togari A., Dickens G., Kuzuya H., Guroff G. The effect of fibroblast growth factor on PC12 cells. J Neurosci. 1985 Feb;5(2):307–316. doi: 10.1523/JNEUROSCI.05-02-00307.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tümmers U., Müller T. H., Schmidt R., Seidl K., Lichtwald K., Vescei P., Wagner H. J., Unsicker K. Destruction of the preganglionic nerves by beta-bungarotoxin does not interfere with normal embryonic development of the rat adrenal medulla. Dev Biol. 1986 Oct;117(2):619–627. doi: 10.1016/0012-1606(86)90330-1. [DOI] [PubMed] [Google Scholar]
  30. Unsicker K., Vey J., Hofmann H. D., Müller T. H., Wilson A. J. C6 glioma cell-conditioned medium induces neurite outgrowth and survival of rat chromaffin cells in vitro: comparison with the effects of nerve growth factor. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2242–2246. doi: 10.1073/pnas.81.7.2242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Walicke P., Cowan W. M., Ueno N., Baird A., Guillemin R. Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci U S A. 1986 May;83(9):3012–3016. doi: 10.1073/pnas.83.9.3012. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES