Gd. Sterne et al., NT-3 MODULATES NPY EXPRESSION IN PRIMARY SENSORY NEURONS FOLLOWING PERIPHERAL-NERVE INJURY, Journal of Anatomy, 193, 1998, pp. 273-281
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.