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.
Petratos
Steven
S
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.
Butzkueven
Helmut
H
Shipham
Kylie
K
Cooper
Helen
H
Bucci
Tamara
T
Reid
Kate
K
Lopes
Elizabeth
E
Emery
Ben
B
Cheema
Surindar S
SS
Kilpatrick
Trevor J
TJ
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