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A BDNF autocrine loop in adult sensory neurons prevents cell death

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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.

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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

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  1. Ann Acheson
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  2. Joanne C. Conover
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  3. James P. Fandl
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  4. Thomas M. DeChiara
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  5. Michelle Russell
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  6. Anu Thadani
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  7. Stephen P. Squinto
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  8. George D. Yancopoulos
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  9. Ronald M. Lindsay
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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

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