Serotonin-immunoreactive neurons and mast cells in the mouse esophagus suggest involvement of serotonin in both motility control and neuroimmune interactions.

Background Serotonin is a major transmitter in the gastrointestinal tract, but little is known about the serotonergic system in the esophagus. Methods The aim of this study was to use multilabel immunofluorescence to characterize serotonin-positive nerve cell bodies and fibers and their relationship with other neuronal and non-neuronal elements in the mouse esophagus. Antibodies against serotonin, vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT), protein gene product 9.5 (PGP 9.5), and alpha-bungarotoxin (alpha-BT), were used. Key Results Serotonin-containing perikarya represented similar to 10% of all PGP 9.5-positive myenteric neurons. Serotonin-positive varicose nerve fibers were found in the lamina muscularis mucosae and present on similar to 13% of alpha-BT-labeled motor endplates in addition to VAChT-immunoreactive motor terminals. As ChAT-positive neurons of the compact formation of the nucleus ambiguus were negative for serotonin, serotonin-positive varicosities on motor endplates are presumed to be of enteric origin. On the other hand, cholinergic ambiguus neurons were densely supplied with serotonin-positive varicosities. The tela submucosa and tunica adventitia contained large numbers of serotonin-positive mast cells, a few of which were in close association with serotonin-positive nerve fibers. Conclusions & Inferences The mouse esophagus is endowed with a rich serotonin-positive intrinsic innervation, including enteric co-innervation of striated muscles. Serotonin may modulate vagal motor innervation of esophageal-striated muscles not only at the central level via projections of the raphe nuclei to the nucleus ambiguus but also at the peripheral level via enteric co-innervation. In addition, mast cells represent a non-neuronal source of serotonin, being involved in neuroimmune processes.