TNFα contributes to the death of NGF-dependent neurons during development
- 29 October 2001
- journal article
- Published by Springer Nature in Nature Neuroscience
- Vol. 4 (12) , 1194-1198
- https://doi.org/10.1038/nn755
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 (TNFalpha) is involved in bringing about the death of NGF-deprived neurons. Function-blocking antibodies against either TNFalpha 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 TNFalpha and TNFR1 during this stage of development, suggesting that TNFalpha acts by an autocrine loop.Keywords
This publication has 22 references indexed in Scilit:
- Soluble TNF receptors partially protect injured motoneurons in the postnatal CNSEuropean Journal of Neuroscience, 2000
- Neurotrophin signal transduction in the nervous systemCurrent Opinion in Neurobiology, 2000
- Induction of cell death by tumour necrosis factor (TNF) receptor 2,CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNFThe EMBO Journal, 1999
- Death Receptors: Signaling and ModulationScience, 1998
- HIV-1 Tat Induces Neuronal Death via Tumor Necrosis Factor-α and Activation of Non-N-methyl-d-aspartate Receptors by a NFκB-Independent MechanismJournal of Biological Chemistry, 1998
- Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive ratNeuroscience Letters, 1996
- Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neuronsCell, 1994
- Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor geneNature, 1994
- The Nerve Growth Factor 35 Years LaterScience, 1987
- Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation.Proceedings of the National Academy of Sciences, 1983