Localization of neurotrophins and their high-affinity receptors during human enteric nervous system development

Background & Aims: Interactions of neurotrophins with the appropriate trk receptors result in growth and maturational alterations in nervous system cells during development. The aim of this study was to examine whether similar interactions could be involved in human enteric nervous system (ENS) survival or differentiation as well. Methods: Immunocytochemical detection of TrkA, TrkB, and TrkC, as well as the ligands neurotrophin 3 (NT-3) and brain-derived neurotrophic factor (BDNF), was accomplished on normal human fetal and postnatal intestine. Results: Neither neurotrophins nor their receptors were identified in immature postmigrational ENS progenitors at 7 weeks' fetal developmental age; however, TrkC and TrkA were specifically localized to developing ENS cells after 19 developmental weeks. From infancy through adulthood, TrkA and TrkB immunoreactivities were localized to both enteric ganglion cells and glia, whereas TrkC was localized exclusively to enteric ganglion cells. In postnatal intestine, BDNF immunoreactivity was primarily localized to enteric ganglion cells, with NT-3 localized to enteric plexuses, intermuscular basal lamina, and along or between circular and longitudinal smooth muscle cells. Conclusions: These data indicate that neurotrophic influences may be involved in ENS development and survival, with potential importance in functional differentiation disorders of the intestinal ENS.