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Letters to Nature
Nature 374, 450 - 453 (30 March 1994); doi:10.1038/374450a0

A BDNF autocrine loop in adult sensory neurons prevents cell death

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

Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707, USA
*Authors to whom correspondence should be addressed
Present address: Alexion Pharmaceuticals Inc., New Haven, Connecticut 06511, USA

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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