Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons

Abstract

In this study the actions of NGF in regulating peptide expression were examined in vivo in adult rat primary sensory neurons. The hypothesis that NGF might tonically inhibit expression of some peptides was tested specifically. In situ hybridization and immunohistochemistry were used to detect presence or absence of alpha-CGRP, beta-CGRP, SP, SOM, VIP, CCK, NPY, and GAL as well as their mRNAs. In neurons in normal lumbar DRG alpha-CGRP, beta-CGRP, SP, and SOM are abundantly and heterogeneously expressed whereas few neurons have detectable VIP, CCK, NPY, or GAL. Two weeks following sciatic nerve transection, concentrations of alpha-CGRP, beta-CGRP, SP, and SOM plus their mRNAs have decreased to background in all but a few neurons. In contrast, VIP, CCK, NPY, and GAL are now synthesized in many neurons. Delayed intrathecal infusion of NGF (125 ng/microliter/hr) for 7 d, starting 2 weeks after injury counteracted the decrease in expression of alpha- CGRP, beta-CGRP and SP expression, but not SOM. This lack of influence of NGF on SOM is consistent with the absence of high-affinity NGF receptors and trk mRNA in SOM-positive neurons. Delayed infusion of NGF also reduced the number of neurons expressing VIP, CCK, NPY, and GAL after injury by approximately one-half in each subpopulation. Therefore, we suggest that NGF suppresses expression of these four peptides but only if the neurons also have NGF receptors. The results show that NGF can regulate peptide expression differentially and may also be part of the signal that allows reversion to normal of responses to injury as axons regenerate.