NT-3 MODULATES NPY EXPRESSION IN PRIMARY SENSORY NEURONS FOLLOWING PERIPHERAL-NERVE INJURY

Peripheral nerve transection induces significant changes in neuropepti de expression and content in injured primary sensory neurons, possibly due to loss of target derived neurotrophic support. This study shows that neurotrophin-3 (NT-3) delivery to the injured nerve influences ne uropeptide Y (NPY) expression within dorsal root ganglia (DRG) neurons . NT-3 was delivered by grafting impregnated fibronectin (500 ng/ml; N T group) in the axotomised sciatic nerve. Animals grafted with plain f ibronectin mats (FN) or nerve grafts (NG) were used as controls. L4 an d L5 DRG from operated and contralateral sides were harvested between 5 and 240 d. Using immunohistochemistry and computerised image analysi s the percentage, diameter and optical density of neurons expressing c alcitonin gene-related peptide (CGRP), substance P (SP), vasoactive in testinal peptide (VIP) and NPY were quantified. Sciatic nerve axotomy resulted in significant reduction in expression of CGRP and SP, and si gnificant upregulation of VIP and NPY (P < 0.05 for ipsilateral vs con tralateral DRG). By d 30, exogenous NT-3 and nerve graft attenuated th e upregulation of NPY (P < 0.05 for NT and NG vs FN). However, NT-3 ad ministration did not influence the expression of CGRP, SP or VIP. The mean cell diameter of NPY immunoreactive neurons was significantly sma ller in the NT-3 group (P < 0.05 for NT vs FN and NG) suggesting a dif ferential influence of NT-3 on larger neurons. The optical densities o f NPY immunoreactive neurons of equal size were the same in each group at any time point, indicating that the neurons responding to NT-3 dow nregulate NPY expression to levels not detectable by immunohistochemis try. These results demonstrate that targeted administration of NT-3 re gulates the phenotype of a NPY-immunoreactive neuronal subpopulation i n the dorsal root ganglia, a further evidence of the trophic role of n eurotrophins on primary sensory neurons.