Overexpression of neural cell adhesion molecule (NCAM) antigens on intestinal smooth muscle in hypoganglionosis: is hypoganglionosis a disorder of the neuromuscular junction?: H. Kobayashi, Z. Li, A. Yamataka, et al. Pediatr Surg Int 19:190–193, (May), 2003

Abstract

Hypoganglionosis (HYP) is a rare condition with a deficiency of nerve cells in the myenteric plexus and a very low level of AchE activity. Because the etiology and pathogenesis is still unknown, the authors looked for anomalies in the field of neuromuscular junctions (NMJ). These junctions are essential for a normal bowel motility. To evaluate NMJ, good markers are synaptophysin (SY), present in neuronal synaptic vesicle membranes and responsible for neurotransmission, and NCAM, which is important for the initial nerve/muscle intercellular adhesion during development and for interaction during synaptogenesis. In 3 boys with HYP, full-thickness biopsy segments were taken from all intestinal segments at the age of 1 to 2 weeks of life. All 3 died within 4 to 7 months. The histologic results were compared with 4 autopsied neonates serving as control. In the normal specimens, NCAM and SY immunoreactivity was strong in both plexus. NCAM- and SY-positive NMJ were identified as moderate in nerve fibers within lamina propria and muscularis mucosae, and many NMJs were associated with nerve fibers in the circular and longitudinal muscle layers. The smooth muscle cells of muscularis mucosae and the inner border of circular muscle layer were negative. In HYP, the plexus showed the same strong immunoreactivity as normal tissue but a lack of expression of NCAM- or SY-positive NMJ was found in all layers. A marked increase of NCAM and SY activity was found in the smooth muscle cells of muscularis mucosae and of the inner border of circular muscle layer. Therefore, in HYP immunoreactivity was irregular in smooth muscle cells but lacking in nerves and NMJs. NCAM is expressed by neuroectodermal tissue and is a marker of mature neural tissue. The lack of marked NMJ together with nerve fibers in the HYP smooth intestinal muscle layers show the absence of neural tissue in these area. The present ganglia stain positively; therefore, the ganglion must be mature, even supported by SY staining. The fact, that NCAM is elevated in special layers of smooth muscle cells and in the NMJ associated with muscle cells, can be explained by disorder of the innervation. The depletion of nerve fibers in the NMJ in HYP suggests a disruption in the contact between nerve and muscle cells. Ganglia that are present in HYP appear to be mature, but neurotransmitter flow from neuron to muscle may be disturbed because contacts between muscle and nerve are disrupted, leading to an accumulation of NCAM in muscle cells and resulting in a disturbance of motility.