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Bcl-2 promotes regeneration of severed axons in mammalian CNS

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Abstract

Most neurons of the mammalian central nervous system (CNS) lose the ability to regenerate severed axons in vivo after a certain point in development1. At least part of this loss in regenerative potential is intrinsic to neurons2–4. Although embryonic retinal ganglion cells (RGCs) can grow axons into tectum of any age, most RGCs from older animals fail to extend axons into CNS tissue derived from donors of any age, including the embryonic tectum2. Here we report that the proto-oncogene bcl-2 plays a key role in this developmental change by promoting the growth and regeneration of retinal axons. This effect does not seem to be an indirect consequence of its well-known anti-apoptotic activity. Another anti-apoptotic drug, ZVAD, supported neuronal survival but did not promote axon regeneration in culture. This finding could lead to new strategies for the treatment of injuries to the CNS.

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References

  1. Aubert, I., Ridet, J.-L. & Gage, F. Curr. Opin. Neurobiol. 5, 625–635 (1995).

    Article  CAS  Google Scholar 

  2. Chen, D. F., Jhaveri, S. & Schneider, G. E. Proc. Natl Acad. Sci. USA 92, 7287–7291 (1995).

    Article  ADS  CAS  Google Scholar 

  3. Shewan, D., Berry, M. & Cohen, J. J. Neurosci. 15, 2057–2062 (1995).

    Article  CAS  Google Scholar 

  4. Aigner, L. et al. Cell 83, 269–278 (1995).

    Article  CAS  Google Scholar 

  5. Perry, V. H., Henderson, Z. & Linden, R. J. Comp. Neurol. 219, 3546–3568 (1983).

    Article  Google Scholar 

  6. Veis, D. J., Sorenson, C. M., Shutter, J. R. & Korsmeyer, S. J. Cell 75, 229–240 (1993).

    Article  CAS  Google Scholar 

  7. Martinou, J.-C. et al. Neuron 13, 1017–1030 (1994).

    Article  CAS  Google Scholar 

  8. Dubois-Dauphin, M., Frankowski, H., Tsujimoto, Y., Huarte, J. & Martinou, J.-C. Proc. Natl Acad. Sci. USA 91, 3309–3313 (1994).

    Article  ADS  CAS  Google Scholar 

  9. Schnell, L. & Schwab, M. E. Nature 343, 269–272 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Angelucci, A., Clascá, F. & Sur, M. J. Neurosci. Methods 65, 101–112 (1996).

    Article  CAS  Google Scholar 

  11. Misantone, L. J., Gershenbaum, M. & Murray, M. J. Neurocytol. 13, 449–465 (1984).

    Article  CAS  Google Scholar 

  12. Davies, A. M. Trends Neurosci. 18, 355–358 (1995).

    Article  CAS  Google Scholar 

  13. Korsmeyer, S. J. Immunol. Today 13, 285–288 (1992).

    Article  CAS  Google Scholar 

  14. Gagliardini, V. et al. Science 263, 826–828 (1994).

    Article  ADS  CAS  Google Scholar 

  15. Miura, M., Zhu, H., Rotello, R., Hartwieg, E. A. & Yuan, J. Cell 75, 653–660 (1993).

    Article  CAS  Google Scholar 

  16. Henkart, P. A. Immunity 4, 195–201 (1996).

    Article  CAS  Google Scholar 

  17. Nicholson, D. W. et al. Nature 376, 37–43 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Fletcher, D. S. et al. J. Interferon Cytokine Res. 15, 243–248 (1995).

    Article  CAS  Google Scholar 

  19. Mansour-Robaey, S., Clarke, D. B., Wang, Y. C., Bray, G. M. & Aguayo, A. J. Proc. Natl Acad. Sci. USA 91, 1632–1636 (1994).

    Article  ADS  CAS  Google Scholar 

  20. Sagot, Y., Tan, S. A., Hammang, J. P., Aebischer, P. & Kato, A. C. J. Neurosci. 16, 2335–2341 (1996).

    Article  CAS  Google Scholar 

  21. Dusart, I. & Sotelo, C. J. Comp. Neurol. 347, 211–232 (1994).

    Article  CAS  Google Scholar 

  22. Young, R. W. J. Comp. Neurol. 229, 362–373 (1984).

    Article  CAS  Google Scholar 

  23. Merry, D. E., Veis, D. J., Hickey, W. F. & Korsmeyer, S. J. Development 120, 301–311 (1994).

    CAS  PubMed  Google Scholar 

  24. Michaelidis, T. M. et al. Neuron 17, 75–89 (1996).

    Article  CAS  Google Scholar 

  25. Zhang, K.-Z., Westberg, J. A., Hölttä, E. & Andersson, L. C. Proc. Natl Acad. Sci. USA 93, 4504–4508 (1996).

    Article  ADS  CAS  Google Scholar 

  26. Fernandez-Sarabia, M. J. & Bischoff, J. R. Nature 366, 274–275 (1993).

    Article  ADS  CAS  Google Scholar 

  27. Wang, H.-G. et al. Oncogene 9, 2751–2756 (1994).

    CAS  Google Scholar 

  28. Greene, L. A. & Kaplan, D. R. Curr. Opin. Neurobiol. 5, 579–587 (1995).

    Article  CAS  Google Scholar 

  29. Meyer-Franke, A., Kaplan, M. R., Pfrieger, F. W. & Barres, B. A. Neuron 15, 805–819 (1995).

    Article  CAS  Google Scholar 

  30. Barres, B. A. et al. Cell 70, 31–46 (1992).

    Article  CAS  Google Scholar 

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Author notes

  1. Jean-Claude Martinou: Glaxo Institute for Molecular Biology, 14 Chemin des Aulx, plan-les-Ouates, 1228 Geneva, Switzerland

Authors and Affiliations

  1. Howard Hughes Medical Institute, Center for Learning and Memory, Center for Cancer Research,

    Dong Feng Chen & Susumu Tonegawa

  2. Departments of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Dong Feng Chen & Susumu Tonegawa

  3. Departments of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Dong Feng Chen, Gerald E. Schneider & Susumu Tonegawa

Authors
  1. Dong Feng Chen
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  2. Gerald E. Schneider
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  3. Jean-Claude Martinou
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  4. Susumu Tonegawa
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Chen, D., Schneider, G., Martinou, JC. et al. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 385, 434–439 (1997). https://doi.org/10.1038/385434a0

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