Overexpression of neural cell adhesion molecule (NCAM) antigens on intestinal smooth muscles in hypoganglionosis: is hypoganglionosis a disorder of the neuromuscular junction?
BACKGROUND
Hypoganglionosis (HP) is characterized histologically by a decreased number of ganglion cells in intestinal myenteric plexuses and functionally by severely impaired gut motility. The purpose of the present study was to investigate the neuromuscular junction (NMJ) in small- and large-intestine biopsy specimens from patients with HP.


METHODS
Fresh frozen sections of small and large intestine from three patients with HP and five age/site-matched controls were examined. All specimens were labeled with neural cell adhesion molecule (NCAM) antibodies and synaptophysin (SY) antibodies to delineate the NMJ.


RESULTS
Normal small- and large-intestine specimens had a moderate number of NCAM-positive NMJ in association with nerve fibers in the lamina propria, muscularis mucosa, and many NCAM-positive NMJ in association with nerve fibers in the circular and longitudinal muscle layers. In HP, there was lack of expression of NCAM-positive NMJ in association with nerve fibers in the lamina propria, muscularis mucosa, and circular and longitudinal muscle layers in both small- and large-intestine specimens, and a marked increase in NCAM expression in the muscularis mucosa and the inner border of the circular muscle layer that was only seen in HP specimens. SY-positive synaptic vesicles were observed throughout the gut in all normal specimens, but there was a lack of SY expression in HP specimens. Expression of NCAM and SY in ganglion cells was the same in all specimens.


CONCLUSIONS
These findings suggest there is a complicated abnormality of the NMJ in HP that may prove to contribute to the disturbances in gut motility seen in this condition.
Kobayashi
Hiroyuki
H
Department of Pediatric Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421 Tokyo, Japan. koba@med.juntendo.ac.jp
Li
Zhixin
Z
Yamataka
Atsuyuki
A
Lane
Geoffrey J
GJ
Miyano
Takeshi
T
D016022:Case-Control Studies; D006627:Hirschsprung Disease / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000473:pathology*
D019006:Neural Cell Adhesion Molecules