title: Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis.
abstract: The gastrointestinal tract is innervated by extrinsic sympathetic, parasympathetic and sensory nerve fibers as well as by intrinsic fibers from the neurons in myenteric and submucosal ganglia embedded into the gastrointestinal wall. Morphological and functional studies of intestinal innervation in animal models are important for understanding the pathophysiology of inflammatory bowel disease (IBD). The recently established Winnie mouse model of spontaneous chronic colitis caused by a point mutation in the Muc2 mucin gene develops inflammation due to a primary epithelial defect. Winnie mice display symptoms of diarrhea, ulcerations and rectal bleeding similar to those in IBD. In this study, we investigated myenteric neurons, noradrenergic, cholinergic and sensory nerve fibers in the distal colon of Winnie (Win/Win) mice compared to C57/BL6 and heterozygote littermates (Win/Wt) using histological and immunohistochemical methods. All Win/Win mice used in this study had inflammation with signs of mucosal damage, goblet cell loss, thickening of muscle and mucosal layers, and increased CD45-immunoreactivity in the distal colon. The density of sensory, cholinergic and noradrenergic fibers innervating the myenteric plexus, muscle and mucosa significantly decreased in the distal colon of Win/Win mice compared to C57/BL6 and Win/Wt mice, while the total number of myenteric neurons as well as subpopulations of cholinergic and nitrergic neurons remained unchanged. In conclusion, changes in the colon morphology and innervation found in Winnie mice have multiple similarities with changes observed in patients with ulcerative colitis.
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Rahman
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Ainsley M
authors.initials: AM
authors.lastname: Robinson
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Jovanovska
authors.affiliation: School of Health Sciences, The University of Tasmania, Launceston, Australia.
authors.forename: Rajaraman
authors.initials: R
authors.lastname: Eri
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia. Kulmira.Nurgali@vu.edu.au.|Western Centre for Health, Research and Education, 176 Furlong Road, St Albans, 3021, Victoria, Australia. Kulmira.Nurgali@vu.edu.au.
authors.forename: Kulmira
authors.identifier: http://orcid.org/0000-0002-2597-6929
authors.initials: K
authors.lastname: Nurgali
mesh_terms: D000818:Animals; D002452:Cell Count; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000150:complications / Q000473:pathology*; D003106:Colon / Q000294:innervation* / Q000473:pathology; D004195:Disease Models, Animal; D005724:Ganglia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D008810:Mice, Inbred C57BL; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism
chemical_list: D052248:Nitric Oxide Synthase Type I
keywords: Distal colon; Innervation; Myenteric neurons; Spontaneous chronic colitis; Winnie mice