DIFFERENTIAL INFLUENCE OF NERVE GROWTH-FACTOR ON NEUROPEPTIDE EXPRESSION IN-VIVO - A NOVEL ROLE IN PEPTIDE SUPPRESSION IN ADULT SENSORY NEURONS

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 test ed specifically. In situ hybridization and immunohistochemistry were u sed to detect presence or absence of alpha-CGRP, beta-CGRP, SP, SOM, V IP, CCK, NPY, and GAL as well as their mRNAs. In neurons in normal lum bar DRG alpha-CGRP, beta-CGRP, SP, and SOM are abundantly and heteroge neously expressed whereas few neurons have detectable VIP, CCK, NPY, o r GAL. Two weeks following sciatic nerve transection, concentrations o f alpha-CGRP, beta-CGRP, SP, and SOM plus their mRNAs have decreased t o 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/mu l/hr) for 7 d, starting 2 weeks after injury counte racted the decrease in expression of alpha-CGRP, beta-CGRP and SP expr ession, but not SOM. This lack of influence of NGF on SOM is consisten t with the absence of high-affinity NGF receptors and trk mRNA in SOM- positive neurons. Delayed infusion of NGF also reduced the number of n eurons expressing VIP, CCK, NPY, and GAL after injury by approximately one-half in each subpopulation. Therefore, we suggest that NGF suppre sses expression of these four peptides but only if the neurons also ha ve NGF receptors. The results show that NGF can regulate peptide expre ssion differentially and may also be part of the signal that allows re version to normal of responses to injury as axons regenerate.