NT-4/5 required for the early growth of regenerating axons in peripheral nerves

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Eur J Neurosci. 2005 May;21(10):2624-34.

Neurotrophin-4/5 is required for the early growth of regenerating

axons in peripheral nerves.

English AW, Meador W, Carrasco DI.

Department of Cell Biology, Emory University School of Medicine,

Atlanta, GA, USA.

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.