Neurotrophin 3 and neurotrophin 4 differentially regulate NCAM, L1 and N-cadherin expression during peripheral nerve regeneration.

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Abstract

The addition of neurotrophin 3 or neurotrophin 4 to injured nerves improves their regeneration potential and may aid axon guidance. It is not well defined whether neurotrophins influence other elements, such as the cell adhesion molecules, that promote nerve guidance and regeneration. Using poly-3-hydroxybutyrate conduits, we applied either neurotrophin 3 or neurotrophin 4 to axotomized rat sciatic nerves and monitored nerve regeneration and cell adhesion molecule expression. Regenerating nerves were stained with antibodies against NCAM and N-cadherin two weeks after injury and staining intensity quantified. NCAM, N-cadherin and L1 transcription was measured in the proximal and distal stumps and ipsilateral dorsal root ganglia (4, 5) using RT-PCR. Both neurotrophins increased NCAM and L1 transcript levels in the dorsal root ganglia of axotomised nerves. This is reflected in the increased NCAM expression at the proximal stump and regeneration front. Increased levels of NCAM were also observed in the distal stump. Neurotrophin 4 administration increased N-cadherin levels proximal to the injury, but not distally. Following neurotrophin 3 administration, N-cadherin expression decreased in proximal and distal stumps compared with control. In conclusion, neurotrophins differentially alter adhesion molecule expression in regenerating nerves and transcription in the corresponding dorsal root ganglia, although these changes in expression do not alter neurotrophin enhanced regeneration. Thus, we propose that retrograde transport of the neurotrophins to the dorsal root ganglia affects adhesion molecule transcription, reflected by protein expression in peripheral nerve axons.

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