Secretory pathways of neuropeptides in XXXX lumbar dorsal root ganglion neurons and effects of peripheral axotomy.

@entity10133 @entity10969 @entity3162 @entity35 @entity4655
Using immunocytochemistry combined with confocal and electron microscopy, the secretory pathways related to substance @entity10133 ), calcitonin gene-related peptide ( @entity4655 ), galanin (GAL), and neuropeptide Y ( @entity10969 ) were investigated in neurons in @entity35 lumbar (L) 4 and L5 dorsal root ganglia (DRGs) before and after peripheral axotomy. All four peptides were processed through the regulated secretory pathway in many small neurons in normal DRGs, and @entity4655 through this pathway also in some large neurons. In many small neurons, two neuropeptides could be sorted into the same or separate large dense-core vesicles (LDCVs). The LDCVs had a significantly larger diameter in small as compared to large DRG neurons. Fourteen days after sciatic nerve cut, the levels of SP- and @entity4655 -like immunoreactivities (-LIs) and the number of LDCVs containing these peptides were markedly reduced, but SP- and @entity4655 -LIs were still seen in the regulated pathway. GAL- @entity3162 was markedly increased in many small neurons and some large neurons and @entity10969 - @entity3162 mainly in large neurons. Both peptides were particularly abundant in the Golgi region. In small neurons, the number of LDCVs containing GAL- or @entity10969 - @entity3162 was increased, but did not appear to reach the numbers containing SP- or @entity4655 - @entity3162 in normal DRG neurons. After axotomy, @entity4655 - @entity3162 and GAL- @entity3162 were often in separate LDCVs. One type of @entity10969 -positive large neurons showed budding off of LDCVs after axotomy, but also some "scattered" labeling in the cytoplasm. In the second type, @entity10969 - @entity3162 was mainly found in multivesicular bodies. In several myelinated nerve fibers a "diffuse" distribution of @entity10969 was seen together with some LDCVs containing @entity10969 - @entity3162 . In contrast, in unmyelinated nerve fibers, @entity10969 -, GAL-, SP-, and @entity4655 -LIs were always observed in LDCVs. Thus, both in normal and axotomized DRG neurons, peptides are processed through the regulated pathway. However, in some large neurons, @entity10969 is, in addition, secreted through the constitutive pathway, perhaps as a consequence of limited sorting mechanisms for @entity10969 , i.e., the plasticity of the secretory mechanisms does not match the rate of peptide synthesis after axotomy.
