Extrinsic innervation of ileum and pelvic flexure of foals with ileocolonic aganglionosis
- 391 Downloads
Equine ileocolonic aganglionosis, which is also called lethal white foal syndrome (LWFS), is a severe congenital condition characterized by the unsuccessful colonization of neural crest progenitors in the caudal part of the small intestine and the entire large intestine. LWFS, which is attributable to a mutation in the endothelin receptor B gene, is the horse equivalent of Hirschsprung’s disease in humans. Affected foals suffer from aganglionosis or hypoganglionosis of the enteric ganglia resulting in intestinal akinesia and colic. In other species with aganglionosis, fibers of extrinsic origin show an abnormal distribution pattern within the gut wall, but we have no information to date regarding this occurrence in horses. Our present aim is to investigate the distribution of extrinsic sympathetic and sensory neural fibers in LWFS, focusing on ileum and the pelvic flexure of the colon of two LWFS foals compared with a control subject. The sympathetic fibers were immunohistochemically identified with the markers tyrosine hydroxylase and dopamine beta-hydroxylase. The extrinsic sensory fibers were identified with the markers Substance P (SP) and calcitonin gene-related peptide (CGRP). Since SP and CGRP are also synthesized by subclasses of horse intramural neurons, LWFS represents a good model for the selective study of extrinsic fiber distribution. Affected foals showed large bundles of extrinsic fibers, compared with the control, as observed in Hirschsprung’s disease. Furthermore, altered adrenergic pathways were observed, prominently in the pelvic flexure. The numbers of SP- and CGRP-immunoreactive fibers in the muscle, a target of enteric neurons, were dramatically reduced, whereas fibers deduced to be extrinsic sensory axons persisted around submucosal blood vessels. Fiber numbers in the mucosa were reduced. Thus, extrinsic innervation, contributing to modulate enteric functions, might also be affected during LWFS.
KeywordsEnteric nervous system Immunohistochemistry Hirschsprung’s disease Lethal white foal syndrome Overo coat pattern
The excellent technical assistance of Dr. Riccardo Rinnovati is gratefully acknowledged.
Compliance with ethical standards
This research was supported by no specific grant from any funding agency in the public, commercial, or not-for-profit sector.
Conflict of interest
The authors declare that they have no conflict of interest.
- Hartig W, Reichenbach A, Voigt C, Boltze J, Bulavina L, Schuhmann MU, Seeger J, Schusser GF, Freytag C, Grosche J (2009) Triple fluorescence labelling of neuronal, glial and vascular markers revealing pathological alterations in various animal models. J Chem Neuroanat 37:128–138CrossRefPubMedGoogle Scholar
- Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Gershon MD, Hutson J, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T (2009) Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group. Acta Neuropathol 118:271–301CrossRefPubMedGoogle Scholar
- Lefebvre D, Hudson NP, Elce YA, Blikslager A, Divers TJ, Handel IG, Tremaine WH, Pirie RS (2015) Clinical features and management of equine postoperative ileus (POI): Survey of Diplomates of the American Colleges of Veterinary Internal Medicine (ACVIM), Veterinary Surgeons (ACVS) and Veterinary Emergency and Critical Care (ACVECC). Equine Vet J. doi: 10.1111/evj.12520 Google Scholar
- Liu JA, Lai FP, Gui HS, Sham MH, Tam PK, Garcia-Barcelo MM, Hui CC, Ngan ES (2015) Identification of GLI mutations in patients with Hirschsprung disease that disrupt enteric nervous system development in mice. Gastroenterology 149:1837-1848. doi: 10.1053/j.gastro.2015.07.060
- Matsumoto K, Hosoya T, Tashima K, Namiki T, Murayama T, Horie S (2011) Distribution of transient receptor potential vanilloid 1 channel-expressing nerve fibers in mouse rectal and colonic enteric nervous system: relationship to peptidergic and nitrergic neurons. Neuroscience 172:518–534CrossRefPubMedGoogle Scholar
- Muniz E, Lobo Ladd AA, Lobo Ladd FV, Silva AA da, Kmit FV, Borges AS, Teixeira R, Mota LS da, Belli CB, Zoppa AL de, Silva LC da, Melo MP de, Coppi AA (2013) 3-D technology used to accurately understand equine ileocolonic aganglionosis. Cells Tissues Organs 198:160–168Google Scholar
- Vrotsos PD, Santschi EM, Purdy AK, Mickelson JR (1999) Incidence of an endothelin receptor B mutation in white patterned horses; evidence for genetic heterogeneity in the Overo coat pattern. Plant & Animal Genomes VII Conference Proceedings, Plant & Animal Genomes VII Conference, San Diego, California, January 18-22, 1999Google Scholar