STUDY FOR MECHANISM OF HYPERTROPHIC EXTRINSIC NERVE FIBER IN DISTAL AGANGLIONIC COLON

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A study of mechanisms for hypertrophic extrinsic nerve fibers in the Hirschsprung's disease colon : Nerve fibers represented with the acetylcholinesterase (AChE) are rich in the distal aganglionic colon of Hirschsprung's disease. The purpose of his study is to clarify this mechanism. The aganglionic colons of both aganglionic rats and Hirschsprung's disease children (provided in an operation) were used. Initially, distribution of the nerve fibers with both frozen section by a microtome and whole-mount preparation was investigated with the anti PGP9.5 antibody, which was a general neural marker. The nerve fibers in the circular muscle layer were not hyperplastic in the aganglionic colon in comparison with control colon. TH, NPY (efferent sympathetic nerve) and VACht (efferent parasympathetic nerve), which were used as marker of the nerve fiber from the pelvic nerve plexus, showed the same in the circular muscle layer. SP and CGRP, which were used as markers for the nerve originated from … More the mesentery (afferent parasympathetic nerve), were poor in the circular muscle layer. In submucosa, these nerve fibers were recognized abundantly in surroundings of the blood vessel. These findings show that there are two kinds of extrinsic nerve fibers in the aganglionic colon. On the other hand, the nerve fibers, which came from a pelvic nerve plexus, were abundant in the submucosa of the distal aganglionic bowel, but the nerve fibers from the mesentery were not. Therefore, increased Ach-E positive nerve mainly traverses in the rectal wall by way of the pelvic *exus, and appears in the submucosal layer of the aganglionic bowel. Then, we studied to clarify the functional aspect of the extrinsic nerve in an aganglionic segment of the colon, using proteins involved in vesicle docking and fusion as a functional marker. Monoclonal antibody for synaptotagmin was prepared as a marker of the soluble NSF (N-rthylmaleimide-sensitive fusion protein) attachment protein receptor (SNARE) in the vesicle and synaptosome-associated protein of Mr 25,000 (SNAP-25) as the SNARE in the target membrane. SNAREs in the submucosa in both the aganglionic segment and control similarly appeared. The nerve fibers in the circular muscle layer of an aganglionic segment showed impaired synaptic vesicle exocytosis related to the vesicle instead of the target membrane.A future examination matter : It is necessary to study receptors of neurotransmission in order to clarify the action to bowel of these nerve fibers in the future. Less