Deletion of p75NTR impairs regeneration of peripheral nerves in mice.
OBJECTIVE
After peripheral nerve injury, p75NTR was upregulated in Schwann cells of the Wallerian degenerative nerves and in motor neurons but down-regulated in the injured sensory neurons. As p75NTR in neurons mediates signals of both neurotrophins and inhibitory factors, it is regarded as a therapeutic target for the treatment of neurodegeneration. However, its physiological function in the nerve regeneration is not fully understood. In the present study, we aimed to examine the role of p75NTR in the regeneration of peripheral nerves.


METHODS
In p75NTR knockout mice (exon III deletion), the sciatic nerves and facial nerves on one side were crushed and regenerating neurons in the facial nuclei and in the dorsal root ganglia were labelled by Fast Blue. The regenerating fibres in the sciatic nerve were also labelled by an anterograde tracer and by immunohistochemistry.


RESULTS
The results showed that the axonal growth of injured axons in the sciatic nerve of p75NTR mutant mice was significantly retarded. The number of regenerated neurons in the dorsal root ganglia and in the facial nuclei in p75NTR mutant mice was significantly reduced. Immunohistochemical staining of regenerating axons also showed the reduction in nerve regeneration in p75NTR mutant mice.


CONCLUSIONS
Our data suggest that p75NTR plays an important role in the regeneration of injured peripheral nerves.
Song
Xing-Yun
XY
Department of Physiology and Centre for Neuroscience, Flinders University, GPO Box 2100, Adelaide 5001, Australia.
Zhang
Feng-He
FH
Zhou
Fiona H
FH
Zhong
Jinhua
J
Zhou
Xin-Fu
XF
D000818:Animals; D001369:Axons / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D019922:GAP-43 Protein / Q000032:analysis; D005727:Ganglia, Spinal / Q000502:physiology; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D009416:Nerve Regeneration; D010525:Peripheral Nerves / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D043222:Ubiquitin Thiolesterase / Q000032:analysis
D019922:GAP-43 Protein; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse; D015740:Calcitonin Gene-Related Peptide