ALTERATIONS IN NEUROTROPHIN AND NEUROTROPHIN-RECEPTOR LOCALIZATION INHIRSCHSPRUNGS-DISEASE

Interactions of the trk family of tyrosine kinase receptors with neuro trophins promote growth and differentiation of nervous-system cells du ring development. Disturbances in neurotrophic signaling could he invo lved in functional or aganglionic conditions of the intestine such as Hirschsprung's disease (HD). Intestinal resection specimens from 20 ch ildren with HD and from 10 normal age-matched controls were evaluated immunocytochemically far the presence of TrkA, TrkB, and TrkC protein, and the neurotrophin ligands brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). All three neurotrophin receptors are local ized with cellular specificity to the enteric nervous system of normal and proximal ganglionic HD intestine; however. none was detected in t he hypertrophic nerve fibers of aganglionic HD segments. Aganglionic H D intestine lacked intense and specific TrkC and BDNF enteric ganglion ic immunoreactivity. NT-3, localized to enteric plexuses and basal lam ina of ganglionic intestine, was not detected in ganglion cells locate d at the ''transitional zone'' of HD intestine. These data suggest tha t neurotrophic influences may be involved in enteric nervous-system ce llular survival and differentiation in functional intestinal disorders such as HD. Copyright (C) 1996 by W.B. Saunders Company.