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Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation
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 dysfunctio...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society of Neurogastroenterology and Motility
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955187/ https://www.ncbi.nlm.nih.gov/pubmed/31715094 http://dx.doi.org/10.5056/jnm19029 |
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author | Swiderski, Kristy Bindon, Rebecka Trieu, Jennifer Naim, Timur Schokman, Shana Swaminathan, Mathusi Leembruggen, Anita J L Hill-Yardin, Elisa L Koopman, René Bornstein, Joel C Lynch, Gordon S |
author_facet | Swiderski, Kristy Bindon, Rebecka Trieu, Jennifer Naim, Timur Schokman, Shana Swaminathan, Mathusi Leembruggen, Anita J L Hill-Yardin, Elisa L Koopman, René Bornstein, Joel C Lynch, Gordon S |
author_sort | Swiderski, Kristy |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6955187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Korean Society of Neurogastroenterology and Motility |
record_format | MEDLINE/PubMed |
spelling | pubmed-69551872020-01-22 Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation Swiderski, Kristy Bindon, Rebecka Trieu, Jennifer Naim, Timur Schokman, Shana Swaminathan, Mathusi Leembruggen, Anita J L Hill-Yardin, Elisa L Koopman, René Bornstein, Joel C Lynch, Gordon S J Neurogastroenterol Motil Original Article 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. Korean Society of Neurogastroenterology and Motility 2020-01 2020-01-30 /pmc/articles/PMC6955187/ /pubmed/31715094 http://dx.doi.org/10.5056/jnm19029 Text en © 2020 The Korean Society of Neurogastroenterology and Motility This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Swiderski, Kristy Bindon, Rebecka Trieu, Jennifer Naim, Timur Schokman, Shana Swaminathan, Mathusi Leembruggen, Anita J L Hill-Yardin, Elisa L Koopman, René Bornstein, Joel C Lynch, Gordon S Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation |
title | Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation |
title_full | Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation |
title_fullStr | Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation |
title_full_unstemmed | Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation |
title_short | Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation |
title_sort | spatiotemporal mapping reveals regional gastrointestinal dysfunction in mdx dystrophic mice ameliorated by oral l-arginine supplementation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955187/ https://www.ncbi.nlm.nih.gov/pubmed/31715094 http://dx.doi.org/10.5056/jnm19029 |
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