X. Zhang et al., SECRETORY PATHWAYS OF NEUROPEPTIDES IN RAT LUMBAR DORSAL-ROOT GANGLION NEURONS AND EFFECTS OF PERIPHERAL AXOTOMY, Journal of comparative neurology, 352(4), 1995, pp. 481-500
Using immunocytochemistry combined with confocal and electron microsco
py, the secretory pathways related to substance P (SP), calcitonin gen
e-related peptide (CGRP), galanin (GAL), and neuropeptide Y (NPY) were
investigated in neurons in rat lumbar (L) 4 and L5 dorsal root gangli
a (DRGs) before and after peripheral axotomy. All four peptides were p
rocessed through the regulated secretory pathway in many small neurons
in normal DRGs, and CGRP through this pathway also in some large neur
ons. In many small neurons, two neuropeptides could be sorted into the
same or separate large dense-core vesicles (LDCVs). The LDCVs had a s
ignificantly larger diameter in small as compared to large DRG neurons
. Fourteen days after sciatic nerve cut, the levels of SP- and CGRP-li
ke immunoreactivities (-LIs) and the number of LDCVs containing these
peptides were markedly reduced, but SP- and CGRP-LIs were still seen i
n the regulated pathway. GAL-LI was markedly increased in many small n
eurons and some large neurons and NPY-LI mainly in large neurons. Both
peptides were particularly abundant in the Golgi region. In small neu
rons, the number of LDCVs containing GAL- or NPY-LI was increased, but
did not appear to reach the numbers containing SP- or CGRP-LI in norm
al DRG neurons. After axotomy, CGRP-LI and GAL-LI were often in separa
te LDCVs. One type of NPY-positive large neurons showed budding off of
LDCVs after axotomy, but also some ''scattered'' labeling in the cyto
plasm. In the second type, NPY-LI was mainly found in multivesicular b
odies. In several myelinated nerve fibers a ''diffuse'' distribution o
f NPY was seen together with some LDCVs containing NPY-LI. In contrast
, in unmyelinated nerve fibers, NPY-, GAL-, SP-, and CGRP-LIs were alw
ays observed in LDCVs. Thus, both in normal and axotomized DRG neurons
, peptides are processed through the regulated pathway. However, in so
me large neurons, NPY is, in addition, secreted through the constituti
ve pathway, perhaps as a consequence of limited sorting mechanisms for
NPY, i.e., the plasticity of the secretory mechanisms does not match
the rate of peptide synthesis after axotomy. (C) 1995 Wiley-Liss, Inc.