Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo

Abstract

NEUROTROPHIN-3 (NT-3)1–4 and neurotrophin-4/5 (NT-4)5–7, together with nerve growth factor and brain-derived neurotrophic factor, are members of the neurotrophin family of proteins8,9, which supports the survival of vertebrate neurons. However, no function in vivo has been described for NT-4 and limited information is available on the role of the other neurotrophins in the central nervous system in vivo. Nerve growth factor prevents the degeneration of lesioned septal cholinergic neurons in the adult brain10–13, whereas brain-derived neurotrophic factor prevents the death of developing motor neurons14–16 and a subpopulation of adult septal cholinergic neurons17. Finally, NT-3 partially prevents the death of facial motor neurons in newborn rats16. To assess the role of NT-3 and NT-4 in the adult brain in vivo, we implanted genetically modified fibroblasts that constitutively express high levels of NT-3 or NT-4. The results show that NT-3, but no other neurotrophin, prevents the degeneration of noradrenergic neurons of the locus coeruleus in a 6-hydroxydopamine lesion model that resembles the pattern of cell loss found in Alzheimer's disease18,19. These results imply that NT-3 may have therapeutic potential for preventing the death of noradrenergic neurons in the locus coeruleus.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hohn, A., Leibrock, J., Bailey, K. & Barde, Y.-A. Nature 344, 339–341 (1990).

    Article  ADS  CAS  Google Scholar 

  2. Maisonpierre, P. C. et al. Science 247, 1446–1451 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Rosenthal, A. et al. Neuron. 4, 767–773 (1990).

    Article  CAS  Google Scholar 

  4. Ernfors, P., Ibanez, C. F., Ebendal, T., Olson, L. & Persson, H. Proc. natn. Acad. Sci. U.S.A. 87, 5454–5458 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Hallböök, F., Ibanez, C. F. & Persson, H. Neuron 6, 845–858 (1991).

    Article  Google Scholar 

  6. Berkemeier, L. R. et al. Neuron 7, 857–866 (1991).

    Article  CAS  Google Scholar 

  7. Ip, N. Y. et al. Proc. natn. Acad. Sci. U.S.A. 89, 3060–3064 (1992).

    Article  ADS  CAS  Google Scholar 

  8. Thoenen, H. Trends Neurosci. 14, 165–179 (1991).

    Article  CAS  Google Scholar 

  9. Persson, H. & Ibanez, C. F. Curr. Opin. Neurol. Neurosurg. 6, 11–18 (1993).

    CAS  PubMed  Google Scholar 

  10. Hefti, F. J. Neurosci. 6, 2155–2162 (1986).

    Article  CAS  Google Scholar 

  11. Williams, L. R. et al. Proc. natn. Acad. Scl. U.S.A. 83, 9231–9235 (1986).

    Article  ADS  CAS  Google Scholar 

  12. Kromer, L. F. Science 235, 214–216 (1987).

    Article  ADS  CAS  Google Scholar 

  13. Rosenberg, M. B. et al. Science 242, 1575–1578 (1988).

    Article  ADS  CAS  Google Scholar 

  14. Yan, Q., Elliott, J. & Snider, W. D. Nature 360, 753–755 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Oppenheim, R. W., Qin-Wei, Y., Prevette, D. & Yan, Q. Nature 360, 755–757 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Sendtner, M., Holtmann, B., Kolbeck, R., Thoenen, M. & Barde, Y.-A. Nature 360, 757–759 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Knüsel, B. et al. J. Neurosci. 12, 4391–4402 (1992).

    Article  Google Scholar 

  18. Chan-Palay, V. Prog. Brain Res. 88, 625–630 (1991).

    Article  CAS  Google Scholar 

  19. German, D. C. et al. Ann. Neurol. 32, 667–676 (1992).

    Article  CAS  Google Scholar 

  20. Westin, G., Gerster, T., Muller, M. M., Schaffner, G. & Schaffner, W. Nucleic. Acids Res. 15, 6787–6798 (1987).

    Article  CAS  Google Scholar 

  21. Ernfors, P. et al. Proc. natn. Acad. Sci. U.S.A. 86, 4756–4760 (1989).

    Article  ADS  CAS  Google Scholar 

  22. Friedman, W. et al. Expl Neurol. 119, 72–78 (1993).

    Article  CAS  Google Scholar 

  23. Merlio, J.-P., Ernfors, P., Jaber, M. & Persson, H. Neuroscience 51, 513–532 (1992).

    Article  CAS  Google Scholar 

  24. Lamballe, F., Klein, R. & Barbacid, M. Cell 66, 967–979 (1991).

    Article  CAS  Google Scholar 

  25. Altar, C. A., Criden, M. R., Lindsay, R. M. & DiStefano, P. S. J. Neurosci. 13, 733–743 (1993).

    Article  CAS  Google Scholar 

  26. Ernfors, P., Wetmore, C., Olson, L. & Persson, H. Neuron 5, 511–526 (1990).

    Article  CAS  Google Scholar 

  27. Phillips, H. S., Halns, H. M., Laramee, G. R., Rosenthal, A. & Winslow J. W. Science 250, 290–294 (1990).

    Article  ADS  CAS  Google Scholar 

  28. Ernfors, P. & Persson, H. Eur. J. Neurosci. 3, 953–961 (1991).

    Article  Google Scholar 

  29. Friedman, W. J., Ernfors, P. & Persson, H. J. Neurosci. 11, 1577–1584 (1991).

    Article  CAS  Google Scholar 

  30. Harley, C. Prog. Brain Res. 88, 307–321 (1991).

    Article  CAS  Google Scholar 

  31. Borgstahl, G. E. O. et al. Cell 71, 107–118 (1992).

    Article  CAS  Google Scholar 

  32. Beal, M. F., Hyman, B. T. & Koroshetz, W. Trends. Neurosci. 16, 125–131 (1993).

    Article  CAS  Google Scholar 

  33. Ibanez, C. F. et al. Development 117, 1345–1353 (1993).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arenas, E., Persson, H. Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature 367, 368–371 (1994). https://doi.org/10.1038/367368a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/367368a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing