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:

A BDNF autocrine loop in adult sensory neurons prevents cell death

Nature volume 374, pages 450–453 (1995)Cite this article

Abstract

DURING the initial phase of their development, sensory neurons of the dorsal root ganglion (DRG) require target-derived trophic support for their survival1–3, but as they mature they lose this requirement. Because many of these neurons express BDNF (brain-derived neurotrophic factor) messenger RNA4,5, we hypo-thesized that BDNF might act as an autocrine survival factor in adult DRG neurons, thus explaining their lack of dependence on exogenous growth factors. When cultured adult DRG cells were treated with antisense oligonucleotides to BDNF, expression of BDNF protein was reduced by 80%, and neuronal survival was reduced by 35%. These neurons could be rescued by exogenous BDNF or neurotrophin-3, but not by other growth factors. Similar results were obtained with single-neuron microcultures, whereas microcultures derived from mutant mice lacking BDNF were unaffected by antisense oligonucleotides. Our results strongly sup-port an autocrine role for BDNF in mediating the survival of a subpopulation of adult DRG neurons.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Lindsay, R. M. J. Neurosci. 8, 2394–2405 (1988).

    Article  CAS  Google Scholar 

  2. Johnson, E. M. & Yip, H. K. Nature 314, 751–752 (1985).

    Article  ADS  CAS  Google Scholar 

  3. Johnson, E. M., Rich, K. M. & Yip, H. K. Trends Neurosci. 9, 33–37 (1986).

    Article  CAS  Google Scholar 

  4. Ernfors, P. et al. Neuron 5, 511–526 (1990).

    Article  CAS  Google Scholar 

  5. Wetmore, C. et al. Expl Neurol. 109, 141–152 (1990).

    Article  CAS  Google Scholar 

  6. Klein, R. et al. Cell 66, 395–403 (1991).

    Article  CAS  Google Scholar 

  7. Soppett, D. et al. Cell 65, 895–903 (1991).

    Article  Google Scholar 

  8. Squinto, S. P. et al. Cell 65, 885–893 (1991).

    Article  CAS  Google Scholar 

  9. McMahon, S. B., Armanini, M. P., Ling, L. H. & Phillips, H. S. Neuron 12, 1161–1171 (1994).

    Article  CAS  Google Scholar 

  10. Becker, D., Meier, C. B. & Herlyn, M. EMBO J. 8, 3685–3691 (1989).

    Article  CAS  Google Scholar 

  11. Morrison, R. S. J. biol. Chem. 266, 728–734 (1991).

    CAS  PubMed  Google Scholar 

  12. Agris, C. H., Blake, K. R., Miller, P. S., Reddy, M. P. & Tsó, P. O. P. Biochemistry 25, 6268–6275 (1986).

    Article  CAS  Google Scholar 

  13. Zamecnik, P. C. & Stephenson, M. L. Proc. natn. Acad. Sci. U.S.A. 75, 280–284 (1978).

    Article  ADS  CAS  Google Scholar 

  14. Wu-Pong, S., Weiss, T. L. & Hunt, C. A. Pharmaceut. Res. 9, 1010–1017 (1992).

    Article  CAS  Google Scholar 

  15. Doherty, P., Mann, D. A. & Walsh, F. S. J. Neurochem. 49, 1676–1687 (1987).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  17. Ip, N. Y. et al. Neuron 10, 137–149 (1993).

    Article  CAS  Google Scholar 

  18. Acheson, A., Barker, P. A., Alderson, R. F., Miller, F. D. & Murphy, R. A. Neuron 7, 265–275 (1991).

    Article  CAS  Google Scholar 

  19. Ernfors, P., Lee, K.-F & Jaenisch, R. Nature 368, 147–150 (1994).

    Article  ADS  CAS  Google Scholar 

  20. Jones, K. R., Fariñas, I., Backus, C. & Reichardt, L. F. Cell 76, 889–999 (1994).

    Article  Google Scholar 

  21. Lindsay, R. M. in Sensory Neurons: Diversity, Development and Plasticity (ed. Scott, S. 404–421 (Oxford Univ. Press, New York, 1992).

    Google Scholar 

  22. Kokaia, Z. et al. Proc. natn. Acad. Sci. U.S.A. 90, 6711–6715 (1993).

    Article  ADS  CAS  Google Scholar 

  23. Schechterson, L. C. & Bothwell, M. Neuron 9, 449–463 (1992).

    Article  Google Scholar 

  24. Wong, V., Arriaga, R., Ip, N. Y. & Lindsay, R. M. Eur. J. Neurosci. 5, 466–474 (1993).

    Article  CAS  Google Scholar 

  25. Hyman, C. et al. Nature 350, 230–232 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Gall, C. M. et al. Molec. cell. Neurosci. 3, 56–63 (1992).

    Article  CAS  Google Scholar 

  27. Ip, N. Y. et al. J. Neurosci. 13, 3394–3405 (1993).

    Article  CAS  Google Scholar 

  28. Phillips, H. S. et al. Neuron 7, 695–702 (1991).

    Article  CAS  Google Scholar 

  29. Klein, R., Conway, D., Parada, L. F. & Barbacid, M. Cell 61, 647–656 (1990).

    Article  CAS  Google Scholar 

  30. Middlemass, D. S., Lindberg, R. A. & Hunter, T. Molec. cell. Biol. 11, 143–153 (1991).

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Stephen P. Squinto

    Present address: Alexion Pharmaceuticals Inc., New Haven, Connecticut, 06511, USA

  2. Ann Acheson and Ronald M. Lindsay: Authors to whom correspondence should be addressed

Authors and Affiliations

  1. Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, New York, 10591-6707, USA

    Ann Acheson, Joanne C. Conover, James P. Fandl, Thomas M. DeChiara, Michelle Russell, Anu Thadani, Stephen P. Squinto, George D. Yancopoulos & Ronald M. Lindsay

Authors
  1. Ann Acheson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joanne C. Conover
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James P. Fandl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas M. DeChiara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michelle Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anu Thadani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephen P. Squinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. George D. Yancopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ronald M. Lindsay
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Acheson, A., Conover, J., Fandl, J. et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 374, 450–453 (1995). https://doi.org/10.1038/374450a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/374450a0

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

Advanced 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