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PLoS Curr. 2015 Jun 26;7. pii: ecurrents.hd.858b4cc7f235df068387e9c20c436a79. doi: 10.1371/currents.hd.858b4cc7f235df068387e9c20c436a79.

Characterization of Gastric Mucosa Biopsies Reveals Alterations in Huntington's Disease.

Author information

1
Department of Experimental Medical Sciences, Brain Disease Biomarker Unit, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
2
Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield Children's NHS Foundation Trust, Sheffield. South Yorkshire, UK.
3
Department of Experimental Medical Science, Lund University, Lund, Sweden.
4
Department of Neurogastroenterology, Experimental Medical Science, Lund University, Lund, Sweden.
5
University of Manchester, Manchester Academic Health Sciences Centre and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
6
School of Biosciences and Medicine, Cardiff University, Cardiff, Wakes, UK.
7
Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, South Yorkshire, UK.
8
Department of Systems Biologym University of Surrey, Guildford, Surrey, UK.
9
Department of Neuropsychiatry, University of Birmingham, Birmingham, West Midlands, UK.
10
Lund University Diabetes Centre, Lund University, Malmö, Sweden.
11
Department of Medical and Molecular Genetics, Kings College London, London, UK.
12
Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
13
Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield Children's NHS foundation Trust, Sheffield, South Yorkshire, UK.

Abstract

Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry. In order to investigate possible histological differences related to gastric acid production, we evaluated the cell density of acid producing parietal cells, as well as gastrin producing cells (the endocrine cell controlling parietal cell function). In addition, we looked at chief cells and somatostatin-containing cells. In gastric mucosa from HD subjects, compared to control subject biopsies, a reduced expression of gastrin (a marker of G cells) was found. This is in line with previous HD mouse studies showing reduction of GI tract neuropeptides.

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