TNFalpha contributes to the death of NGF-dependent neurons during development.
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.
Barker
V
V
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, Summerhall Square, Edinburgh EH9 1QH, Scotland.
Middleton
G
G
Davey
F
F
Davies
A M
AM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D020932:Nerve Growth Factor / Q000172:deficiency*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics
D000906:Antibodies; D015703:Antigens, CD; D018696:Neuroprotective Agents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor