Abstract
The present immunohistochemical study was designed to investigate the manner of the myenteric nerve regeneration and expression of glial cell line-derived neurotrophic factor (GDNF) and its signaling receptor (Ret) in nerves after transection of the muscle coat (myectomy) in the rat small intestine. The enteric neurons and enteroglial cells were immunohistochemically determined using antibodies against protein gene product 9.5 and S-100 protein, respectively. The neuronal sprouts issued from the severed nerve stumps 12 h after the operation, and thereafter extended into the lesion. The proximal portions of outgrowing neuronal fibers were gradually enveloped by regenerating enteroglial cells to become thick nerve bundles. The regrowing neurons and their associated enteroglial cells developed into an irregular network in the myectomized area on postoperative day 5. The elongation of the regrowing nerves was conspicuously accelerated from postoperative day 3 in accordance with the regrowing neurons started to associate with the enteroglial cells. Under normal conditions, faint immunoreactivity for GDNF and Ret was selectively localized in the enteroglial cells and neurons within the myenteric ganglia, respectively. Following myectomy, the both immunoreactivities were significantly intensified in the nerve stumps and ganglia proximal to the lesion. The regenerating enteroglial cells in the lesion, being in close association with the regrowing neurons, exhibited a dense immunoreaction to GDNF, whereas the neuronal fibers were richly supplied with reaction products of Ret in their entire course. The present findings suggest that the enteroglial cells, contacting with regrowing neurons, may promote the myenteric nerve regeneration in the rat small intestine, via the GDNF-Ret signaling system.
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