Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 29, Issue 7, Pages -Publisher
WILEY
DOI: 10.1111/nmo.13045
Keywords
5-hydroxytryptamine receptor type 4; enteric nervous system; lethal white foal syndrome; prokinetic; serotonin
Funding
- Italian Ministry of Public Health (Ricerca Finalizzata RER -Ita-MNGIE)
- Italian Ministry of University and Research [PRIN/COFIN 2009MFSXNZ_002]
- Telethon grant [GGP15171]
- Fondazione del Monte di Bologna e Ravenna, Bologna, Italy
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Background: Serotonin plays a pivotal role in regulating gut motility, visceral sensitivity, and fluid secretion via specific receptors. Among these receptors, 5-HT4 exerts a prominent control on gut motor function. Although the prokinetic effect exerted by 5-HT4 agonists is well known, the cellular sites of 5-HT4 expression remain poorly understood in large mammals, e.g., horses. In this study, we evaluated the distribution of 5-HT4 in the horse intestine and in foals with enteric aganglionosis, reminiscent of human Hirschsprung's disease. Methods: The intestine and spinal ganglia were obtained from three healthy horses and two foals with hereditary ileocolonic aganglionosis. Tissues were processed for immunohistochemistry using a specific antibody to 5-HT4 and a variety of neuronal markers. Myenteric and submucosal plexus 5-HT4-immunoreactive (IR) neurons were quantified as relative percentage (meanSD) to the total number of neurons counted. Furthermore, the density of 5-HT4-IR nerve fibers was evaluated in the mucosa and tunica muscularis. Key Results: The 5-HT4 immunoreactivity was localized to large percentages of myenteric neurons ranging from 28 +/- 9% (descending colon) to 63 +/- 19% (ileum), and submucosal neurons ranging from 54 +/- 6% (ileum) to 68 +/- 14% (duodenum). The 5-HT4-immunoreactivity was co-expressed by some substance P-IR (SP-IR) spinal ganglion neurons and extrinsic sensory fibers of aganglionic foals. Conclusions & Inferences: The presence of 5-HT4 in many enteric and extrinsic sensory neurons and nerve fibers provides solid morphological evidence of the cellular sites of 5-HT4 expression in horses. The evidence of SP-IR sensory neurons positive for 5-HT4 suggests its role in visceral sensitivity.
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