Physiology - Research Publications

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    Colonic dilation and altered ex vivo gastrointestinal motility in the neuroligin-3 knockout mouse
    Leembruggen, AJL ; Balasuriya, GK ; Zhang, J ; Schokman, S ; Swiderski, K ; Bornstein, JC ; Nithianantharajah, J ; Hill-Yardin, EL (WILEY, 2020-05)
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    Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation
    Swiderski, K ; Bindon, R ; Trieu, J ; Naim, T ; Schokman, S ; Swaminathan, M ; Leembruggen, AJL ; Hill-Yardin, EL ; Koopman, R ; Bornstein, JC ; Lynch, GS (KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY, 2020-01)
    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.
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    The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders
    Herath, M ; Hosie, S ; Bornstein, JC ; Franks, AE ; Hill-Yardin, EL (FRONTIERS MEDIA SA, 2020-05-28)
    Mucus is integral to gut health and its properties may be affected in neurological disease. Mucus comprises a hydrated network of polymers including glycosylated mucin proteins. We propose that factors that influence the nervous system may also affect the volume, viscosity, porosity of mucus composition and subsequently, gastrointestinal (GI) microbial populations. The gut has its own intrinsic neuronal network, the enteric nervous system, which extends the length of the GI tract and innervates the mucosal epithelium. The ENS regulates gut function including mucus secretion and renewal. Both dysbiosis and gut dysfunction are commonly reported in several neurological disorders such as Parkinson's and Alzheimer's disease as well in patients with neurodevelopmental disorders including autism. Since some microbes use mucus as a prominent energy source, changes in mucus properties could alter, and even exacerbate, dysbiosis-related gut symptoms in neurological disorders. This review summarizes existing knowledge of the structure and function of the mucus of the GI tract and highlights areas to be addressed in future research to better understand how intestinal homeostasis is impacted in neurological disorders.