J Neurogastroenterol Motil  https://doi.org/10.5056/jnm19029
Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation
Kristy Swiderski,1 Rebecka Bindon,1 Jennifer Trieu,1 Timur Naim,1 Shana Schokman,2Mathusi Swaminathan,2 Anita J L Leembruggen,2 Elisa L Hill-Yardin,2,3 René Koopman,1Joel C Bornstein,2 and Gordon S Lynch1*
1Centre for Muscle Research, Department of Physiology, School of Biomedical Sciences, The University of Melbourne, Australia; 2Enteric Nervous System Laboratory, Department of Physiology, The University of Melbourne, Australia; and 3Gut-Brain Axis Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia (Current address)
Correspondence to: Gordon S Lynch, PhD
Department of Physiology, The University of Melbourne, Building 181, Crn. Grattan St and Royal Pde, Parkville, VIC 3010, Australia
Tel: +613-8344-0065, Fax: +613-8344-5818, E-mail: gsl@unimelb.edu.au
Received: February 13, 2019; Revised: July 9, 2019; Accepted: July 23, 2019; Published online: November 13, 2019.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

Abstract
Background/Aims
Patients with Duchenne muscular dystrophy exhibit significant, ongoing impairments in gastrointestinal (GI) function likely resulting from dysregulated nitric oxide production. Compounds increasing neuronal nitric oxide synthase expression and/or activity could improve GI dysfunction and enhance quality of life for dystrophic patients. We used video imaging and spatiotemporal mapping to identify GI dysfunction in mdx dystrophic mice and determine whether dietary intervention to enhance nitric oxide could alleviate aberrant colonic activity in muscular dystrophy.
Methods
Four-week-old male C57BL/10 and mdx mice received a specialized diet either with no supplementation (control) or supplemented (1 g/kg/day) with L-alanine, L-arginine, or L-citrulline for 8 weeks. At the conclusion of treatment, mice were sacrificed by cervical dislocation and colon motility examined by spatiotemporal (ST) mapping ex vivo.
Results
ST mapping identified increased contraction number in the mid and distal colon of mdx mice on control and L-alanine supplemented diets relative to C57BL/10 mice (P < 0.05). Administration of either L-arginine or L-citrulline attenuated contraction number in distal colons of mdx mice relative to C57BL/10 mice.
Conclusions
GI dysfunction in Duchenne muscular dystrophy has been sadly neglected as an issue affecting quality of life. ST mapping identified regional GI dysfunction in the mdx dystrophic mouse. Dietary interventions to increase nitric oxide signaling in the GI tract reduced the number of colonic contractions and alleviated colonic constriction at rest. These findings in mdx mice reveal that L-arginine can improve colonic motility and has potential therapeutic relevance for alleviating GI discomfort, improving clinical care, and enhancing quality of life in Duchenne muscular dystrophy.
Keywords: Arginine; Duchenne; Gastrointestinal diseases; Muscular dystrophy, Duchenne; Nitric oxide synthase type I, colon


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