Neurotrophin-4/5 is required for the early growth of regenerating axons in peripheral nerves.
The requirement of the trkB ligand, neurotrophin-4/5 (NT-4/5), for the growth of regenerating axons in the peripheral nervous system (PNS) is not well established. We studied regenerating axon growth in transected peripheral nerves of thy-1-YFP-H mice that had been repaired using allografts obtained from brain-derived neurotrophic factor (BDNF) or NT-4/5 knockout mice. Lengths of profiles of YFP+ axons measured in these grafts were compared with those measured in grafts obtained from wild-type donors. When compared with axon profiles measured in grafts from wild-type donors, axon profile lengths measured in grafts from homozygous (NT-4/5(-/-)) or heterozygous (NT-4/5(+/-)) mice were significantly shorter. In contrast, the lengths of axon profiles measured in grafts from BDNF(+/-) mice were not significantly different from those measured in grafts from wild-type mice. A reduced amount of BDNF, but not NT-4/5, is sufficient to promote the elongation of regenerating axons in the PNS. When grafts from wild-type or NT-4/5(-/-) mice were treated acutely at the time of surgical repair either with exogenous BDNF or NT-4/5, the lengths of axon profiles measured in the grafts were significantly longer than those measured in grafts from untreated wild-type mice. These findings are consistent with a requirement for NT-4/5 from within the pathway used by regenerating axons for the successful growth of those axons in peripheral nerves.
English
Arthur W
AW
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA. art@cellbio.emory.edu
Meador
William
W
Carrasco
Dario I
DI
D000818:Animals; D001369:Axons / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D017930:Genes, Reporter; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D018696:Neuroprotective Agents; D012584:Sciatic Nerve / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C071951:neurotrophin 5; C073922:neurotrophin 4