Anorectal Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington’s Disease

Kobal, Jan; Kolenc, Matej; Koželj, Matic; Podnar, Simon

doi:10.3233/jhd-170280

Cited by 15 publications

(12 citation statements)

References 23 publications

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“…Alongside progressive central pathology resulting in neurodegeneration and cognitive decline 3 , 4 , HD pathology is defined by weight loss 27 – 29 . It has been pointed out that presymptomatic mutation carriers and patients with Huntington's disease show upper GI tract problems 30 , bladder 31 and bowel dysfunction 32 and that the severity of dysfunction correlates with poor quality of life and depression. Similarly, van der Burg and colleagues found impaired gut motility, diarrhea, and malabsorption of food in R6/2 mice 9 .…”

Section: Discussionmentioning

confidence: 99%

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

Stan

Soylu-Kucharz

Burleigh

et al. 2020

Sci Rep

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Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.

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Section: Discussionmentioning

confidence: 99%

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

Stan

Soylu-Kucharz

Burleigh

et al. 2020

Sci Rep

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show abstract

“…HD is the only disease in the group in which gastrointestinal (GI) dysfunction is a major symptom. Signs of this dysfunction can appear early, before evidence of CNS neurodegeneration is apparent ( Kobal et al, 2018 ; Wood et al, 2008 ; Andrich et al, 2009 ). Similar symptoms are seen in mouse models of HD where they are associated with a decrease in the length of the colon ( Stan et al, 2020 ), the mucosal thickness and villus length ( van der Burg et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models

Zhao

McHugh

Coffey

et al. 2022

Disease Models &Amp; Mechanisms

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Repeat expansion diseases (REDs) are a large group of human genetic disorders caused by expansion of a specific short tandem repeat sequence. Expansion in somatic cells affects age at onset and disease severity in some of these disorders. However, alleles in blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system (CNS) in both humans and mouse models. Here we examined the extent of expansion in different DNA sources from mouse models of the Fragile X related disorders (FXDs), Huntington's disease (HD), Spinocerebellar ataxia type 1 (SCA1) and Spinocerebellar ataxia type 2 (SCA2). We found that stool is a much better indicator of somatic expansion than blood. Since stool is a sensitive and non-invasive source of DNA, it may be useful for studies of factors affecting expansion risk or the monitoring of treatments aimed at reducing expansion in preclinical trials since it would allow expansions to be examined longitudinally in the same animal and allow significant effects to be ascertained much earlier than is possible with other DNA sources.

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“…Anorectal dysfunction, manifesting as incontinence or constipation, is significantly more prevalent in individuals with HD compared with healthy controls and may even arise in the premanifest stage 66 . Several studies have shown no evidence of degeneration in Onuf's nucleus, although anal sphincter EMG studies do demonstrate decreased tonic sphincter activity and impaired voluntary activation 67 …”

Section: Primary Movement Disorders With Associated Gi Symptomsmentioning

confidence: 99%

Movement Disorders and the Gut: A Review

Talman

Pfeiffer

2022

Movement Disord Clin Pract

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There is a close link between multiple movement disorders and gastrointestinal dysfunction. Gastrointestinal symptoms may precede the development of the neurologic syndrome or may arise following the neurologic presentation. This review will provide an overview of gastrointestinal accompaniments to several well‐known as well as lesser known movement disorders. It will also highlight several disorders which may not be considered primary movement disorders but have an overlapping presentation of both gastrointestinal and movement abnormalities.

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Anorectal Dysfunction in Presymptomatic Mutation Carriers and Patients with Huntington’s Disease

Abstract: Our study demonstrated significant bowel dysfunction in HD patients. We propose these symptoms to be of central autonomic origin, although we cannot exclude effects of medication. These often neglected symptoms in HD subjects require greater attention from physicians.

Cited by 15 publications

References 23 publications

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models

Movement Disorders and the Gut: A Review

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