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

Abstract

Serotonin is a major transmitter in the gastrointestinal tract, but little is known about the serotonergic system in the esophagus. 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 α-bungarotoxin (α-BT), were used. Serotonin-containing perikarya represented ∼10% of all PGP 9.5-positive myenteric neurons. Serotonin-positive varicose nerve fibers were found in the lamina muscularis mucosae and present on ∼13% of α-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. 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.