Skip to main content
NCBI 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 Dec;84(23):8735–8739. doi: 10.1073/pnas.84.23.8735

Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages.

R Heumann 1, D Lindholm 1, C Bandtlow 1, M Meyer 1, M J Radeke 1, T P Misko 1, E Shooter 1, H Thoenen 1
PMCID: PMC299621  PMID: 2825206

Abstract

In newborn rats the levels of nerve growth factor (NGF) mRNA (mRNANGF) and NGF receptor mRNA (mRNA(rec)) in the sciatic nerve were 10 and 120 times higher, respectively, than in adult animals. mRNA(rec) levels decreased steadily from birth, approaching adult levels by the third postnatal week, whereas mRNANGF levels decreased only after the first postnatal week, although also reaching adult levels by the third week. Transection of the adult sciatic nerve resulted in a marked biphasic increase in mRNANGF with time. On the proximal side of the cut, this increase was confined to the area immediately adjacent to the cut; peripherally, a similar biphasic increase was present in all segments. mRNA(rec) levels were also markedly elevated distal to the transection site, in agreement with previous results obtained by immunological methods [Taniuchi, M., Clark, H. B. & Johnson, E. M., Jr. (1986) Proc. Natl. Acad. Sci. USA 83, 4094-4098]. Following a crush lesion (allowing regeneration), the mRNA(rec) levels were rapidly down-regulated as the regenerating nerve fibers passed through the distal segments. Down-regulation of mRNANGF also occurred during regeneration but was slower and not as extensive as that of mRNA(rec) over the time period studied. Changes in mRNANGF and mRNA(rec) occurring in vivo after transection were compared with those observed in pieces of sciatic nerve kept in culture. No difference was found for mRNA(rec). Only the initial rapid increase in mRNANGF occurred in culture, but the in vivo situation could be mimicked by the addition of activated macrophages. This reflects the situation in vivo where, after nerve lesion, macrophages infiltrate the area of the Wallerian degeneration. These results suggest that mRNANGF synthesis in sciatic non-neuronal cells is regulated by macrophages, whereas mRNA(rec) synthesis is determined by axonal contact.

Full text

PDF
8735

Selected References

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

  1. Acheson A. L., Naujoks K., Thoenen H. Nerve growth factor-mediated enzyme induction in primary cultures of bovine adrenal chromaffin cells: specificity and level of regulation. J Neurosci. 1984 Jul;4(7):1771–1780. doi: 10.1523/JNEUROSCI.04-07-01771.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bandtlow C. E., Heumann R., Schwab M. E., Thoenen H. Cellular localization of nerve growth factor synthesis by in situ hybridization. EMBO J. 1987 Apr;6(4):891–899. doi: 10.1002/j.1460-2075.1987.tb04835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beuche W., Friede R. L. The role of non-resident cells in Wallerian degeneration. J Neurocytol. 1984 Oct;13(5):767–796. doi: 10.1007/BF01148493. [DOI] [PubMed] [Google Scholar]
  4. Billett E. E., Gunn B., Mayer R. J. Characterization of two monoclonal antibodies obtained after immunization with human liver mitochondrial membrane preparations. Biochem J. 1984 Aug 1;221(3):765–776. doi: 10.1042/bj2210765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  7. Ebendal T., Olson L., Seiger A. The level of nerve growth factor (NGF) as a function of innervation. A correlation radio-immunoassay and bioassay study of the rat iris. Exp Cell Res. 1983 Oct 15;148(2):311–317. doi: 10.1016/0014-4827(83)90155-6. [DOI] [PubMed] [Google Scholar]
  8. Greene L. A., Shooter E. M. The nerve growth factor: biochemistry, synthesis, and mechanism of action. Annu Rev Neurosci. 1980;3:353–402. doi: 10.1146/annurev.ne.03.030180.002033. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Heumann R., Thoenen H. Comparison between the time course of changes in nerve growth factor protein levels and those of its messenger RNA in the cultured rat iris. J Biol Chem. 1986 Jul 15;261(20):9246–9249. [PubMed] [Google Scholar]
  11. Ignatius M. J., Gebicke-Härter P. J., Skene J. H., Schilling J. W., Weisgraber K. H., Mahley R. W., Shooter E. M. Expression of apolipoprotein E during nerve degeneration and regeneration. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1125–1129. doi: 10.1073/pnas.83.4.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Korsching S., Thoenen H. Quantitative demonstration of the retrograde axonal transport of endogenous nerve growth factor. Neurosci Lett. 1983 Aug 19;39(1):1–4. doi: 10.1016/0304-3940(83)90155-6. [DOI] [PubMed] [Google Scholar]
  14. Levi-Montalcini R., Angeletti P. U. Nerve growth factor. Physiol Rev. 1968 Jul;48(3):534–569. doi: 10.1152/physrev.1968.48.3.534. [DOI] [PubMed] [Google Scholar]
  15. Mosier D. E. Separation of macrophages on plastic and glass surfaces. Methods Enzymol. 1984;108:294–297. doi: 10.1016/s0076-6879(84)08094-0. [DOI] [PubMed] [Google Scholar]
  16. Müller H. W., Ignatius M. J., Hangen D. H., Shooter E. M. Expression of specific sheath cell proteins during peripheral nerve growth and regeneration in mammals. J Cell Biol. 1986 Feb;102(2):393–402. doi: 10.1083/jcb.102.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Perry V. H., Brown M. C., Gordon S. The macrophage response to central and peripheral nerve injury. A possible role for macrophages in regeneration. J Exp Med. 1987 Apr 1;165(4):1218–1223. doi: 10.1084/jem.165.4.1218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Radeke M. J., Misko T. P., Hsu C., Herzenberg L. A., Shooter E. M. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature. 1987 Feb 12;325(6105):593–597. doi: 10.1038/325593a0. [DOI] [PubMed] [Google Scholar]
  19. Richardson P. M., Ebendal T. Nerve growth activities in rat peripheral nerve. Brain Res. 1982 Aug 19;246(1):57–64. doi: 10.1016/0006-8993(82)90141-x. [DOI] [PubMed] [Google Scholar]
  20. Rush R. A. Immunohistochemical localization of endogenous nerve growth factor. Nature. 1984 Nov 22;312(5992):364–367. doi: 10.1038/312364a0. [DOI] [PubMed] [Google Scholar]
  21. Stoll G., Müller H. W. Macrophages in the peripheral nervous system and astroglia in the central nervous system of rat commonly express apolipoprotein E during development but differ in their response to injury. Neurosci Lett. 1986 Dec 23;72(3):233–238. doi: 10.1016/0304-3940(86)90519-7. [DOI] [PubMed] [Google Scholar]
  22. Taniuchi M., Clark H. B., Johnson E. M., Jr Induction of nerve growth factor receptor in Schwann cells after axotomy. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4094–4098. doi: 10.1073/pnas.83.11.4094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Thoenen H., Barde Y. A. Physiology of nerve growth factor. Physiol Rev. 1980 Oct;60(4):1284–1335. doi: 10.1152/physrev.1980.60.4.1284. [DOI] [PubMed] [Google Scholar]
  24. Webster H. D., Martin R., O'Connell M. F. The relationships between interphase Schwann cells and axons before myelination: a quantitative electron microscopic study. Dev Biol. 1973 Jun;32(2):401–416. doi: 10.1016/0012-1606(73)90250-9. [DOI] [PubMed] [Google Scholar]
  25. Zimmermann A., Sutter A. beta-Nerve growth factor (beta NGF) receptors on glial cells. Cell-cell interaction between neurones and Schwann cells in cultures of chick sensory ganglia. EMBO J. 1983;2(6):879–885. doi: 10.1002/j.1460-2075.1983.tb01517.x. [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