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
. 1991 Feb 1;88(3):961–965. doi: 10.1073/pnas.88.3.961

Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3.

B Knüsel 1, J W Winslow 1, A Rosenthal 1, L E Burton 1, D P Seid 1, K Nikolics 1, F Hefti 1
PMCID: PMC50934  PMID: 1992488

Abstract

Recombinant human brain-derived neurotrophic factor (rhBDNF) and neurotrophin 3 (rhNT-3), two recently cloned molecules closely related to nerve growth factor (NGF), were produced from human cDNA expressed in human embryonic kidney cells. The recombinant proteins were tested in cultures of dissociated fetal rat brain cells containing basal forebrain cholinergic neurons. rhBDNF stimulated the differentiation of the cholinergic neurons, similar to NGF, which is well established as a neurotrophic factor for these cells. However, rhBDNF was particularly effective during the first few days in vitro, whereas the stimulatory action of rhNGF was more pronounced later in the development of the cultures. This finding indicates the existence of different time periods of responsiveness of the cholinergic neurons to BDNF and NGF. To assess the selectivity of the effect of rhBDNF on cholinergic neurons, its actions were tested in cultures of ventral mesencephalon containing dopaminergic cells. In contrast to NGF, which does not affect central dopaminergic neurons, rhBDNF increased dopamine uptake activity. The findings suggest that BDNF stimulates survival or differentiation of other cells besides the cholinergic neurons.

Full text

PDF
961

Images in this article

963Image
on p.963
963Image
on p.963
963Image
on p.963
963Image
on p.963
963Image
on p.963
963Image
on p.963
963Image
on p.963
963Image
on p.963

Selected References

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

  1. Ayer-LeLievre C., Olson L., Ebendal T., Seiger A., Persson H. Expression of the beta-nerve growth factor gene in hippocampal neurons. Science. 1988 Jun 3;240(4857):1339–1341. doi: 10.1126/science.2897715. [DOI] [PubMed] [Google Scholar]
  2. Barde Y. A., Davies A. M., Johnson J. E., Lindsay R. M., Thoenen H. Brain derived neurotrophic factor. Prog Brain Res. 1987;71:185–189. doi: 10.1016/s0079-6123(08)61823-3. [DOI] [PubMed] [Google Scholar]
  3. Barde Y. A. Trophic factors and neuronal survival. Neuron. 1989 Jun;2(6):1525–1534. doi: 10.1016/0896-6273(89)90040-8. [DOI] [PubMed] [Google Scholar]
  4. Bottenstein J. E., Sato G. H. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979 Jan;76(1):514–517. doi: 10.1073/pnas.76.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. Denis-Donini S., Glowinski J., Prochiantz A. Specific influence of striatal target neurons on the in vitro outgrowth of mesencephalic dopaminergic neurites: a morphological quantitative study. J Neurosci. 1983 Nov;3(11):2292–2299. doi: 10.1523/JNEUROSCI.03-11-02292.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dreyfus C. F., Peterson E. R., Crain S. M. Failure of nerve growth factor to affect fetal mouse brain stem catecholaminergic neurons in culture. Brain Res. 1980 Aug 4;194(2):540–547. doi: 10.1016/0006-8993(80)91239-1. [DOI] [PubMed] [Google Scholar]
  8. Ernfors P., Ibáez C. F., Ebendal T., Olson L., Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454–5458. doi: 10.1073/pnas.87.14.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ferrari G., Minozzi M. C., Toffano G., Leon A., Skaper S. D. Basic fibroblast growth factor promotes the survival and development of mesencephalic neurons in culture. Dev Biol. 1989 May;133(1):140–147. doi: 10.1016/0012-1606(89)90305-9. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Hatanaka H., Tsukui H., Nihonmatsu I. Developmental change in the nerve growth factor action from induction of choline acetyltransferase to promotion of cell survival in cultured basal forebrain cholinergic neurons from postnatal rats. Brain Res. 1988 Mar 1;467(1):85–95. doi: 10.1016/0165-3806(88)90069-7. [DOI] [PubMed] [Google Scholar]
  12. Hefti F., Hartikka J., Knusel B. Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases. Neurobiol Aging. 1989 Sep-Oct;10(5):515–533. doi: 10.1016/0197-4580(89)90118-8. [DOI] [PubMed] [Google Scholar]
  13. Hofer M., Pagliusi S. R., Hohn A., Leibrock J., Barde Y. A. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J. 1990 Aug;9(8):2459–2464. doi: 10.1002/j.1460-2075.1990.tb07423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hohn A., Leibrock J., Bailey K., Barde Y. A. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990 Mar 22;344(6264):339–341. doi: 10.1038/344339a0. [DOI] [PubMed] [Google Scholar]
  15. Knusel B., Michel P. P., Schwaber J. S., Hefti F. Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J Neurosci. 1990 Feb;10(2):558–570. doi: 10.1523/JNEUROSCI.10-02-00558.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koh S., Loy R. Localization and development of nerve growth factor-sensitive rat basal forebrain neurons and their afferent projections to hippocampus and neocortex. J Neurosci. 1989 Sep;9(9):2999–0318. doi: 10.1523/JNEUROSCI.09-09-02999.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Large T. H., Weskamp G., Helder J. C., Radeke M. J., Misko T. P., Shooter E. M., Reichardt L. F. Structure and developmental expression of the nerve growth factor receptor in the chicken central nervous system. Neuron. 1989 Feb;2(2):1123–1134. doi: 10.1016/0896-6273(89)90179-7. [DOI] [PubMed] [Google Scholar]
  18. Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., Barde Y. A. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. doi: 10.1038/341149a0. [DOI] [PubMed] [Google Scholar]
  19. Lindsay R. M., Thoenen H., Barde Y. A. Placode and neural crest-derived sensory neurons are responsive at early developmental stages to brain-derived neurotrophic factor. Dev Biol. 1985 Dec;112(2):319–328. doi: 10.1016/0012-1606(85)90402-6. [DOI] [PubMed] [Google Scholar]
  20. Maisonpierre P. C., Belluscio L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., Yancopoulos G. D. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451. doi: 10.1126/science.247.4949.1446. [DOI] [PubMed] [Google Scholar]
  21. Martínez H. J., Dreyfus C. F., Jonakait G. M., Black I. B. Nerve growth factor selectively increases cholinergic markers but not neuropeptides in rat basal forebrain in culture. Brain Res. 1987 Jun 2;412(2):295–301. doi: 10.1016/0006-8993(87)91136-x. [DOI] [PubMed] [Google Scholar]
  22. Michel P. P., Dandapani B. K., Knusel B., Sanchez-Ramos J., Hefti F. Toxicity of 1-methyl-4-phenylpyridinium for rat dopaminergic neurons in culture: selectivity and irreversibility. J Neurochem. 1990 Apr;54(4):1102–1109. doi: 10.1111/j.1471-4159.1990.tb01935.x. [DOI] [PubMed] [Google Scholar]
  23. Michel P. P., Dandapani B. K., Sanchez-Ramos J., Efange S., Pressman B. C., Hefti F. Toxic effects of potential environmental neurotoxins related to 1-methyl-4-phenylpyridinium on cultured rat dopaminergic neurons. J Pharmacol Exp Ther. 1989 Feb;248(2):842–850. [PubMed] [Google Scholar]
  24. Mobley W. C., Rutkowski J. L., Tennekoon G. I., Buchanan K., Johnston M. V. Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. Science. 1985 Jul 19;229(4710):284–287. doi: 10.1126/science.2861660. [DOI] [PubMed] [Google Scholar]
  25. Morrison R. S., Kornblum H. I., Leslie F. M., Bradshaw R. A. Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor. Science. 1987 Oct 2;238(4823):72–75. doi: 10.1126/science.3498986. [DOI] [PubMed] [Google Scholar]
  26. Phillips H. S., Hains J. M., Laramee G. R., Rosenthal A., Winslow J. W. Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons. Science. 1990 Oct 12;250(4978):290–294. doi: 10.1126/science.1688328. [DOI] [PubMed] [Google Scholar]
  27. Prochiantz A., Daguet M. C., Herbet A., Glowinski J. Specific stimulation of in vitro maturation of mesencephalic dopaminergic neurones by striatal membranes. Nature. 1981 Oct 15;293(5833):570–572. doi: 10.1038/293570a0. [DOI] [PubMed] [Google Scholar]
  28. Rennert P. D., Heinrich G. Nerve growth factor mRNA in brain: localization by in situ hybridization. Biochem Biophys Res Commun. 1986 Jul 31;138(2):813–818. doi: 10.1016/s0006-291x(86)80569-1. [DOI] [PubMed] [Google Scholar]
  29. Rodriguez-Tébar A., Dechant G., Barde Y. A. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron. 1990 Apr;4(4):487–492. doi: 10.1016/0896-6273(90)90107-q. [DOI] [PubMed] [Google Scholar]
  30. Rosenthal A., Goeddel D. V., Nguyen T., Lewis M., Shih A., Laramee G. R., Nikolics K., Winslow J. W. Primary structure and biological activity of a novel human neurotrophic factor. Neuron. 1990 May;4(5):767–773. doi: 10.1016/0896-6273(90)90203-r. [DOI] [PubMed] [Google Scholar]
  31. Schatteman G. C., Gibbs L., Lanahan A. A., Claude P., Bothwell M. Expression of NGF receptor in the developing and adult primate central nervous system. J Neurosci. 1988 Mar;8(3):860–873. doi: 10.1523/JNEUROSCI.08-03-00860.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shalaby I. A., Kotake C., Hoffmann P. C., Heller A. Release of dopamine from coaggregate cultures of mesencephalic tegmentum and corpus striatum. J Neurosci. 1983 Aug;3(8):1565–1571. doi: 10.1523/JNEUROSCI.03-08-01565.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thoenen H., Bandtlow C., Heumann R. The physiological function of nerve growth factor in the central nervous system: comparison with the periphery. Rev Physiol Biochem Pharmacol. 1987;109:145–178. doi: 10.1007/BFb0031026. [DOI] [PubMed] [Google Scholar]
  34. Vantini G., Schiavo N., Di Martino A., Polato P., Triban C., Callegaro L., Toffano G., Leon A. Evidence for a physiological role of nerve growth factor in the central nervous system of neonatal rats. Neuron. 1989 Sep;3(3):267–273. doi: 10.1016/0896-6273(89)90251-1. [DOI] [PubMed] [Google Scholar]
  35. Walicke P. A. Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions. J Neurosci. 1988 Jul;8(7):2618–2627. doi: 10.1523/JNEUROSCI.08-07-02618.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Whittemore S. R., Seiger A. The expression, localization and functional significance of beta-nerve growth factor in the central nervous system. Brain Res. 1987 Nov;434(4):439–464. doi: 10.1016/0165-0173(87)90008-7. [DOI] [PubMed] [Google Scholar]
  37. Yan Q., Johnson E. M., Jr An immunohistochemical study of the nerve growth factor receptor in developing rats. J Neurosci. 1988 Sep;8(9):3481–3498. doi: 10.1523/JNEUROSCI.08-09-03481.1988. [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