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TNFα contributes to the death of NGF-dependent neurons during development

Nature Neuroscience volume 4, pages 1194–1198 (2001)Cite this article

Abstract

Many sympathetic and sensory neurons depend on a supply of nerve growth factor (NGF) from their targets during development, and neurons that fail to obtain sufficient NGF die by apoptosis. Here we show that tumor necrosis factor alpha (TNFα) is involved in bringing about the death of NGF-deprived neurons. Function-blocking antibodies against either TNFα or TNF receptor 1 (TNFR1) rescued many sympathetic and sensory neurons following NGF deprivation in vitro. Fewer sympathetic and sensory neurons died during the phase of naturally occurring neuronal death in TNF-deficient embryos, and neurons from these embryos survived in culture better than wild-type neurons. These neurons coexpress TNFα and TNFR1 during this stage of development, suggesting that TNFα acts by an autocrine loop.

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Figure 1: Survival of E16 SCG and trigeminal neurons cultured with NGF, TNFα and function-blocking TNFα or TNFR1 antibodies after NGF deprivation.
Figure 2: E16 SCG and trigeminal neuron dose responses to NGF and TNFα.
Figure 3: In vitro survival of SCG and trigeminal neurons from TNF-deficient and wild-type embryos.
Figure 4: Number of pyknotic neurons and total numbers of neurons in the SCG and trigeminal of E16 and P1 TNFα+/+ and TNFα−/− mice.
Figure 5: Expression of TNFα and TNFR1 by cultured SCG neurons.

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Acknowledgements

This work was supported by grants from the Wellcome Trust and European Commission.

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Authors and Affiliations

  1. Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, Summerhall Square, EH9 1QH, Edinburgh, Scotland

    Victoria Barker, Gayle Middleton & Alun M. Davies

  2. School of Biomedical Sciences, Bute Medical Buildings, University of St. Andrews, St. Andrews, KY16 9AT, Fife, Scotland

    Fleur Davey

  3. Rinat Neuroscience Corporation, 3155 Porter Drive, Palo Alto, 94304, California, USA

    Alun M. Davies

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  1. Victoria Barker
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Correspondence to Alun M. Davies.

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Barker, V., Middleton, G., Davey, F. et al. TNFα contributes to the death of NGF-dependent neurons during development. Nat Neurosci 4, 1194–1198 (2001). https://doi.org/10.1038/nn755

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