Get access

Role of Bcl-2 in the Brain-derived Neurotrophic Factor Survival Response

Authors

  • Timothy E. Allsopp,

    1. School of Biological and Medical Sciences, Bute Medical Building, St Andrews University, St Andrews, Fife KY16 9TS, UK
    Search for more papers by this author
    • 1

      Department of Veterinary Pathology, The Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK

  • Sergei Kiselev,

    1. School of Biological and Medical Sciences, Bute Medical Building, St Andrews University, St Andrews, Fife KY16 9TS, UK
    Search for more papers by this author
  • Sean Wyatt,

    1. School of Biological and Medical Sciences, Bute Medical Building, St Andrews University, St Andrews, Fife KY16 9TS, UK
    Search for more papers by this author
    • 2

      Department of Molecular Pathology, Windeyer Building, University College London, London, UK

  • Alun M. Davies

    Corresponding author
    1. School of Biological and Medical Sciences, Bute Medical Building, St Andrews University, St Andrews, Fife KY16 9TS, UK
    Search for more papers by this author

  • Acknowledgements

Correspondence to: A. M. Davies

Abstract

Developing neurons die if they fail to obtain an adequate supply of neurotrophins from their targets but how neurotrophins suppress cell death is not known. Although over-expression of exogenous Bcl-2 can prevent the death of cultured neurons deprived of members of the nerve growth factor family of neurotrophins it is not known if this effect is physiologically relevant. To determine if Bcl-2 participates in the neurotrophin survival response we used antisense bcl-2 RNA to inhibit endogenous Bcl-2 expression. Here we show that brain-derived neurotrophic factor (BDNF)-dependent neurons are killed by antisense bcl-2 RNA in the presence of BDNF. However, when these neurons were supported with ciliary neurotrophic factor (CNTF) their survival was not affected by antisense bcl-2 RNA. Likewise, the survival of CNTF-dependent ciliary neurons was not affected by antisense bcl-2 RNA. Our findings suggest that Bcl-2 is required for the BDNF survival response and that alternative, Bcl-2-independent survival mechanisms operate in sensory and parasympathetic neurons exposed to CNTF.

Ancillary