Alterations in neurotrophin and neurotrophin-receptor localization in Hirschsprung's disease

Interactions of the trk family of tyrosine kinase receptors with neurotrophins promote growth and differentiation of nervous-system cells during development. Disturbances in neurotrophic signalling could be involved in functional or aganglionic conditions of the intestine such as Hirschsprung's disease (HD). Intestinal resection specimens from 20 children with HD and from 10 normal age-matched controls were evaluated immunocytochemically for 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 localized with cellular specificity to the enteric nervous system of normal and proximal ganglionic HD intestine; however, none was detected in the hypertrophic nerve fibers of aganglionic HD segments. Aganglionic HD intestine lacked intense and specific TrkC and BDNF enteric ganglionic immunoreactivity. NT-3, localized to enteric plexuses and basal lamina of ganglionic intestine, was not detected in ganglion cells located at the "transitional zone" of HD intestine. These data suggest that neurotrophic influences may be involved in enteric nervous-system cellular survival and differentiation in functional intestinal disorders such as HD.