Schwann cell apoptosis in the postnatal axotomized sciatic nerve is mediated via NGF through the low-affinity neurotrophin receptor.
Schwann cell death is a developmentally regulated phenomenon and is also induced after peripheral nerve axotomy in neonatal rodents. In this study, we explored whether ligand-induced activation of the low-affinity neurotrophin receptor (p75(NTR)) is responsible for inducing Schwann cell death in vivo. Administration of exogenous nerve growth factor (NGF) to the axotomized nerve site in wild-type animals resulted in a 2.6-fold increase in Schwann cell apoptosis in the distal nerve stumps compared to axotomy alone. No increase in apoptosis, above baseline levels, was seen in p75(NTR)-mutant mice either with or without NGF When anti-NGF antibodies were administered to the site of the peripheral nerve lesion in wild-type mice there was a reduction in the percentage of Schwann cell apoptosis to levels seen in both the quiescent state and in the axotomized nerves of the p75(NTR)-mutant mice. These results demonstrate that apoptosis of Schwann cells in axotomized peripheral nerve is mediated predominantly through p75(NTR) signaling and initiated via endogenously produced NGF.
Development and Neurobiology Group, The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Post Office, The Royal Melbourne Hospital. Victoria, Australia.
Steven
S
Petratos
Helmut
H
Butzkueven
Kylie
K
Shipham
Helen
H
Cooper
Tamara
T
Bucci
Kate
K
Reid
Elizabeth
E
Lopes
Ben
B
Emery
Surindar S
SS
Cheema
Trevor J
TJ
Kilpatrick
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D019771:Axotomy; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000254:growth & development / Q000293:injuries* / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D009418:S100 Proteins; D020932:Nerve Growth Factor