QUALITATIVE AND QUANTITATIVE-ANALYSIS OF SYNAPSES IN HIRSCHSPRUNGS-DISEASE

In Hirschsprung's disease (HD), certain intestinal nervous plexuses ar e absent. Sprouting nerve endings contain different amounts of synapto physin (SY), a protein and main constituent of acetylcholinesterase (A ChE) storage compartments. Due to the lack of specific markers for syn apses, a qualitative analysis of nerve endings of intestinal segments affected by HD has not yet been undertaken. For this study, resected c olorectal specimens from patients with HD (n = 8, mean age 2.1 years) were investigated in parallel for AChE, SY, and content of small synap tic vesicles by biochemical, immunohistochemical, and electronmicrosco pic means. In the microdissected muscular layer, reduced SY (1.4 mu g/ mg total protein, normal 24 +/- 0.3) was observed Immunohistochemistry showed in affected tissues reduced numbers of SY-positive nerve fiber s and nerve endings, which in turn were thickened and distorted, in bo th the muscle proper and the muscularis mucosae. Combining both morpho logic and biochemical findings, in HD the number of cholinergic vesicl es in the remaining nerve endings seems to be increased as measured by SY, a marker molecule specific for synaptic vesicles. Our data also s uggest that nerve endings in HD may contain high concentrations of cho linergic vesicles, paralleling the known high amounts of acetylcholine and AChE found in intestinal segments of patients with HD.