Re-expression of p75NTR by adult motor neurons after axotomy is triggered by retrograde transport of a positive signal from axons regrowing through damaged or denervated peripheral nerve tissue

Neuroscience. 1999;91(1):273-81. doi: 10.1016/s0306-4522(98)00562-4.

Abstract

To investigate different types of potential signalling mechanisms that regulate neuronal reactions to axotomizing injury, we compared the re-expression of the low-affinity neurotrophin receptor, p75NTR, and the down-regulation of choline acetyltransferase expression, after various combinations of axotomy, crush injury and blockade of axonal transport in adult hypoglossal motor neurons in the rat. We found that pure axotomy in the absence of crush injury down-regulated choline acetyltransferase, but did not induce p75NTR re-expression. Blockade of axonal transport with colchicine had an identical effect. In contrast, both a crush injury on its own, or a crush injury proximal to a complete axotomy, induced p75NTR re-expression and down-regulated expression of choline acetyltransferase. Blockade of axonal transport with colchicine or tight ligation proximal to a crush prevented the crush injury-induced re-expression of p75NTR. Infusion of vehicle, nerve growth factor or ciliary neurotrophic factor induced low levels of p75NTR re-expression that were not significantly different from each other and were substantially lower than crush-induced levels. These findings confirm previous suggestions that the loss of choline acetyltransferase expression is due to the interruption of a constitutive retrograde signal, and show that the re-expression of p75NTR by adult motor neurons after axotomy is triggered by the retrograde transport of a positive signal derived from axons that are regrowing through damaged or denervated peripheral nerve tissue. The precise source and nature of this signal are not yet clear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Axotomy
  • Choline O-Acetyltransferase / metabolism
  • Ciliary Neurotrophic Factor
  • Colchicine / pharmacology
  • Female
  • Immunohistochemistry
  • Motor Neurons / metabolism*
  • Muscle Denervation
  • Nerve Crush
  • Nerve Growth Factors / pharmacology
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins / pharmacology
  • Peripheral Nerves / physiology*
  • Rats
  • Rats, Wistar
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor / biosynthesis*
  • Signal Transduction / physiology*

Substances

  • Ciliary Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Choline O-Acetyltransferase
  • Colchicine