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Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis

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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.

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Acknowledgments

This study was supported by the Australian National Health & Medical Research Council project grant 1032414 and a Victoria University research support grant.

Conflict of interest

The authors of this manuscript do not have any potential conflicts to disclose.

Role of authors

AAR performed experiments, analyzed data and wrote the manuscript. AMR performed experiments, analyzed data and contributed to manuscript writing. VJ contributed to processing tissues for immunohistochemical and histological studies. RE and KN developed the concept and edited manuscript. KN obtained funding and supervised the study.

Funding

This study is supported by the Australian National Health & Medical Research Council project grant 1032414 and a Victoria University Research Development Grant.

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Authors and Affiliations

  1. Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, Australia

    Ahmed A. Rahman, Ainsley M. Robinson, Valentina Jovanovska & Kulmira Nurgali

  2. School of Health Sciences, The University of Tasmania, Launceston, Australia

    Rajaraman Eri

  3. Western Centre for Health, Research and Education, 176 Furlong Road, St Albans, 3021, Victoria, Australia

    Kulmira Nurgali

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  1. Ahmed A. Rahman
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Correspondence to Kulmira Nurgali.

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Rahman, A.A., Robinson, A.M., Jovanovska, V. et al. Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis. Cell Tissue Res 362, 497–512 (2015). https://doi.org/10.1007/s00441-015-2251-3

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