Abstract
In Hirschsprung's disease (HD), certain intestinal nervous plexuses are absent. Sprouting nerve endings contain different amounts of synaptophysin (SY), a protein and main constituent of acetylcholinesterase (AChE) storage compartments. Due to the lack of specific markers for synapses, a qualitative analysis of nerve endings of intestinal segments affected by HD has not yet been undertaken. For this study, resected colorectal specimens from patients with HD (n = 8, mean age 2.1 years) were investigated in parallel for AChE, SY, and content of small synaptic vesicles by biochemical, immunohistochemical, and electronmicroscopic means. In the microdissected muscular layer, reduced SY (1.4 microgram/mg total protein, normal 24 +/- 0.3) was observed. Immunohistochemistry showed in affected tissues reduced numbers of SY-positive nerve fibers and nerve endings, which in turn were thickened and distorted, in both the muscle proper and the muscularis mucosae. Combining both morphologic and biochemical findings, in HD the number of cholinergic vesicles in the remaining nerve endings seems to be increased as measured by SY, a marker molecule specific for synaptic vesicles. Our data also suggest that nerve endings in HD may contain high concentrations of cholinergic vesicles, paralleling the known high amounts of acetylcholine and AChE found in intestinal segments of patients with HD.
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