TY - JOUR
T1 - Gastrointestinal dysfunction contributes to weight loss in Huntington's disease mice
AU - van der Burg, Jorien M. M.
AU - Winqvist, Annika
AU - Aziz, N. Ahmad
AU - Maat-Schieman, Marion L. C.
AU - Roos, Raymund A. C.
AU - Bates, Gillian P.
AU - Brundin, Patrik
AU - Bjorkqvist, Maria
AU - Wierup, Nils
PY - 2011/10
Y1 - 2011/10
N2 - Weight loss is the most important non-neurological complication of Huntington's disease (HD). It correlates with disease progression and affects the quality of life of HD patients, suggesting that it could be a valuable target for therapeutic intervention. The mechanism underlying weight loss in HD is unknown. Mutant huntingtin, the protein that causes the disease, is not only expressed in the brain, but also along the gastrointestinal (GI) tract. Here we demonstrate that the Cl tract of HD mice is affected. At the anatomical level we observed loss of enteric neuropeptides, as well as decreased mucosal thickness and villus length. Exploring the functions of the Cl system we found impaired gut motility, diarrhea, and malabsorption of food. The degree of malabsorption was inversely associated with body weight, suggesting that GI dysfunction plays an important role in weight loss in HD mice. In summary, these observations suggest that the GI tract is affected in HD mice and that GI dysfunction contributes to nutritional deficiencies and weight loss. (C) 2011 Elsevier Inc. All rights reserved.
AB - Weight loss is the most important non-neurological complication of Huntington's disease (HD). It correlates with disease progression and affects the quality of life of HD patients, suggesting that it could be a valuable target for therapeutic intervention. The mechanism underlying weight loss in HD is unknown. Mutant huntingtin, the protein that causes the disease, is not only expressed in the brain, but also along the gastrointestinal (GI) tract. Here we demonstrate that the Cl tract of HD mice is affected. At the anatomical level we observed loss of enteric neuropeptides, as well as decreased mucosal thickness and villus length. Exploring the functions of the Cl system we found impaired gut motility, diarrhea, and malabsorption of food. The degree of malabsorption was inversely associated with body weight, suggesting that GI dysfunction plays an important role in weight loss in HD mice. In summary, these observations suggest that the GI tract is affected in HD mice and that GI dysfunction contributes to nutritional deficiencies and weight loss. (C) 2011 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.nbd.2011.05.006
DO - 10.1016/j.nbd.2011.05.006
M3 - Article
VL - 44
SP - 1
EP - 8
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -
