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. 1994 Sep 13;91(19):8812–8816. doi: 10.1073/pnas.91.19.8812

Murine oligodendroglial cells express nerve growth factor.

S Byravan 1, L M Foster 1, T Phan 1, A N Verity 1, A T Campagnoni 1
PMCID: PMC44696  PMID: 8090729

Abstract

The studies reported here present evidence for the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) by an oligodendroglial cell line and of NGF by oligodendrocytes in mouse primary culture. An immortalized oligodendroglial cell line (N19) expressing markers for immature oligodendrocytes stimulated PC12 cells to elaborate processes. Polymerase chain reaction analysis with degenerate primers indicated that the N19 cells expressed the mRNAs for the neurotrophic factors NGF and BDNF. Northern blot analysis confirmed that the N19 cells expressed the 1.3-kb NGF mRNA and the 1.4- and 4-kb BDNF mRNAs. In situ hybridization histochemistry identified the presence of NGF mRNAs in 9-day primary oligodendroglial cultures. Combined immunocytochemistry and in situ hybridization histochemistry colocalized NGF mRNA within primary cultured cells that immunostained for the oligodendrocyte marker galactocerebroside (GC). Double-immunofluorescence analysis also colocalized NGF protein within GC+ cells and within A2B5+ cells, a marker for oligodendrocyte progenitors. These results show that oligodendroglia and their precursor cells can express the neurotrophic factor NGF. They suggest that cells in the oligodendrocyte lineage may play an active role in neurite extension through fiber tracts in addition to myelination.

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Selected References

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

  1. Amur-Umarjee S. G., Dasu R. G., Campagnoni A. T. Temporal expression of myelin-specific components in neonatal mouse brain cultures: evidence that 2',3'-cyclic nucleotide 3'-phosphodiesterase appears prior to galactocerebroside. Dev Neurosci. 1990;12(4-5):251–262. doi: 10.1159/000111854. [DOI] [PubMed] [Google Scholar]
  2. Amur-Umarjee S., Phan T., Campagnoni A. T. Myelin basic protein mRNA translocation in oligodendrocytes is inhibited by astrocytes in vitro. J Neurosci Res. 1993 Sep 1;36(1):99–110. doi: 10.1002/jnr.490360111. [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. Barde Y. A. The nerve growth factor family. Prog Growth Factor Res. 1990;2(4):237–248. doi: 10.1016/0955-2235(90)90021-b. [DOI] [PubMed] [Google Scholar]
  5. Bazan J. F. Neuropoietic cytokines in the hematopoietic fold. Neuron. 1991 Aug;7(2):197–208. doi: 10.1016/0896-6273(91)90258-2. [DOI] [PubMed] [Google Scholar]
  6. Berkemeier L. R., Winslow J. W., Kaplan D. R., Nikolics K., Goeddel D. V., Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991 Nov;7(5):857–866. doi: 10.1016/0896-6273(91)90287-a. [DOI] [PubMed] [Google Scholar]
  7. Caroni P., Schwab M. E. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol. 1988 Apr;106(4):1281–1288. doi: 10.1083/jcb.106.4.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chao M. V. Neurotrophin receptors: a window into neuronal differentiation. Neuron. 1992 Oct;9(4):583–593. doi: 10.1016/0896-6273(92)90023-7. [DOI] [PubMed] [Google Scholar]
  9. Clegg D. O., Large T. H., Bodary S. C., Reichardt L. F. Regulation of nerve growth factor mRNA levels in developing rat heart ventricle is not altered by sympathectomy. Dev Biol. 1989 Jul;134(1):30–37. doi: 10.1016/0012-1606(89)90075-4. [DOI] [PubMed] [Google Scholar]
  10. Davies A. M., Bandtlow C., Heumann R., Korsching S., Rohrer H., Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. 1987 Mar 26-Apr 1Nature. 326(6111):353–358. doi: 10.1038/326353a0. [DOI] [PubMed] [Google Scholar]
  11. Di Marco E., Mathor M., Bondanza S., Cutuli N., Marchisio P. C., Cancedda R., De Luca M. Nerve growth factor binds to normal human keratinocytes through high and low affinity receptors and stimulates their growth by a novel autocrine loop. J Biol Chem. 1993 Oct 25;268(30):22838–22846. [PubMed] [Google Scholar]
  12. Eves E. M., Tucker M. S., Roback J. D., Downen M., Rosner M. R., Wainer B. H. Immortal rat hippocampal cell lines exhibit neuronal and glial lineages and neurotrophin gene expression. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4373–4377. doi: 10.1073/pnas.89.10.4373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Foster L. M., Phan T., Verity A. N., Bredesen D., Campagnoni A. T. Generation and analysis of normal and shiverer temperature-sensitive immortalized cell lines exhibiting phenotypic characteristics of oligodendrocytes at several stages of differentiation. Dev Neurosci. 1993;15(2):100–109. doi: 10.1159/000111322. [DOI] [PubMed] [Google Scholar]
  14. Furukawa S., Furukawa Y., Satoyoshi E., Hayashi K. Synthesis and secretion of nerve growth factor by mouse astroglial cells in culture. Biochem Biophys Res Commun. 1986 Apr 14;136(1):57–63. doi: 10.1016/0006-291x(86)90876-4. [DOI] [PubMed] [Google Scholar]
  15. Gold B. G., Mobley W. C., Matheson S. F. Regulation of axonal caliber, neurofilament content, and nuclear localization in mature sensory neurons by nerve growth factor. J Neurosci. 1991 Apr;11(4):943–955. doi: 10.1523/JNEUROSCI.11-04-00943.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gonzalez D., Dees W. L., Hiney J. K., Ojeda S. R., Saneto R. P. Expression of beta-nerve growth factor in cultured cells derived from the hypothalamus and cerebral cortex. Brain Res. 1990 Mar 19;511(2):249–258. doi: 10.1016/0006-8993(90)90169-c. [DOI] [PubMed] [Google Scholar]
  17. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heumann R., Korsching S., Bandtlow C., Thoenen H. Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol. 1987 Jun;104(6):1623–1631. doi: 10.1083/jcb.104.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Heumann R., Korsching S., Scott J., Thoenen H. Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues. EMBO J. 1984 Dec 20;3(13):3183–3189. doi: 10.1002/j.1460-2075.1984.tb02277.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Johnson E. M., Jr, Taniuchi M., DiStefano P. S. Expression and possible function of nerve growth factor receptors on Schwann cells. Trends Neurosci. 1988 Jul;11(7):299–304. doi: 10.1016/0166-2236(88)90090-2. [DOI] [PubMed] [Google Scholar]
  21. Kokaia Z., Bengzon J., Metsis M., Kokaia M., Persson H., Lindvall O. Coexpression of neurotrophins and their receptors in neurons of the central nervous system. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6711–6715. doi: 10.1073/pnas.90.14.6711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Korsching S., Thoenen H. Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3513–3516. doi: 10.1073/pnas.80.11.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Laywell E. D., Steindler D. A. Boundaries and wounds, glia and glycoconjugates. Cellular and molecular analyses of developmental partitions and adult brain lesions. Ann N Y Acad Sci. 1991;633:122–141. doi: 10.1111/j.1749-6632.1991.tb15603.x. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987 Sep 4;237(4819):1154–1162. doi: 10.1126/science.3306916. [DOI] [PubMed] [Google Scholar]
  26. Lin L. F., Doherty D. H., Lile J. D., Bektesh S., Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993 May 21;260(5111):1130–1132. doi: 10.1126/science.8493557. [DOI] [PubMed] [Google Scholar]
  27. Logan A., Frautschy S. A., Gonzalez A. M., Sporn M. B., Baird A. Enhanced expression of transforming growth factor beta 1 in the rat brain after a localized cerebral injury. Brain Res. 1992 Aug 7;587(2):216–225. doi: 10.1016/0006-8993(92)91000-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maisonpierre P. C., Belluscio L., Friedman B., Alderson R. F., Wiegand S. J., Furth M. E., Lindsay R. M., Yancopoulos G. D. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron. 1990 Oct;5(4):501–509. doi: 10.1016/0896-6273(90)90089-x. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Martin D. L. Synthesis and release of neuroactive substances by glial cells. Glia. 1992;5(2):81–94. doi: 10.1002/glia.440050202. [DOI] [PubMed] [Google Scholar]
  31. Miranda R. C., Sohrabji F., Toran-Allerand C. D. Neuronal colocalization of mRNAs for neurotrophins and their receptors in the developing central nervous system suggests a potential for autocrine interactions. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6439–6443. doi: 10.1073/pnas.90.14.6439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Murphy R. A., Oger J., Saide J. D., Blanchard M. H., Arnason B. G., Hogan C., Pantazis N. J. Secretion of nerve growth factor by central nervous system glioma cells in culture. J Cell Biol. 1977 Mar;72(3):769–773. doi: 10.1083/jcb.72.3.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Palmatier M. A., Hartman B. K., Johnson E. M., Jr Demonstration of retrogradely transported endogenous nerve growth factor in axons of sympathetic neurons. J Neurosci. 1984 Mar;4(3):751–756. doi: 10.1523/JNEUROSCI.04-03-00751.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rabizadeh S., Oh J., Zhong L. T., Yang J., Bitler C. M., Butcher L. L., Bredesen D. E. Induction of apoptosis by the low-affinity NGF receptor. Science. 1993 Jul 16;261(5119):345–348. doi: 10.1126/science.8332899. [DOI] [PubMed] [Google Scholar]
  35. Raff M. C., Mirsky R., Fields K. L., Lisak R. P., Dorfman S. H., Silberberg D. H., Gregson N. A., Leibowitz S., Kennedy M. C. Galactocerebroside is a specific cell-surface antigenic marker for oligodendrocytes in culture. Nature. 1978 Aug 24;274(5673):813–816. [PubMed] [Google Scholar]
  36. Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schwab M. E., Caroni P. Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J Neurosci. 1988 Jul;8(7):2381–2393. doi: 10.1523/JNEUROSCI.08-07-02381.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Suzumura A., Bhat S., Eccleston P. A., Lisak R. P., Silberberg D. H. The isolation and long-term culture of oligodendrocytes from newborn mouse brain. Brain Res. 1984 Dec 24;324(2):379–383. doi: 10.1016/0006-8993(84)90054-4. [DOI] [PubMed] [Google Scholar]
  39. Verity A. N., Bredesen D., Vonderscher C., Handley V. W., Campagnoni A. T. Expression of myelin protein genes and other myelin components in an oligodendrocytic cell line conditionally immortalized with a temperature-sensitive retrovirus. J Neurochem. 1993 Feb;60(2):577–587. doi: 10.1111/j.1471-4159.1993.tb03188.x. [DOI] [PubMed] [Google Scholar]
  40. Wheeler E. F., Bothwell M. Spatiotemporal patterns of expression of NGF and the low-affinity NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis. J Neurosci. 1992 Mar;12(3):930–945. doi: 10.1523/JNEUROSCI.12-03-00930.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yamakuni T., Ozawa F., Hishinuma F., Kuwano R., Takahashi Y., Amano T. Expression of beta-nerve growth factor mRNA in rat glioma cells and astrocytes from rat brain. FEBS Lett. 1987 Oct 19;223(1):117–121. doi: 10.1016/0014-5793(87)80520-3. [DOI] [PubMed] [Google Scholar]
  42. Zafra F., Hengerer B., Leibrock J., Thoenen H., Lindholm D. Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors. EMBO J. 1990 Nov;9(11):3545–3550. doi: 10.1002/j.1460-2075.1990.tb07564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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