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Increased thirst and drinking in Huntington's disease and the R6/2 mouse

Wood, Nigel I.; Goodman, Anna O. G.; van der Burg, Jorien m LU ; Gazeau, Veronique; Brundin, Patrik LU ; Björkqvist, Maria LU ; Petersen, Asa; Tabrizi, Sarah J.; Barker, Roger A. and Morton, A. Jennifer (2008) In Brain Research Bulletin 76(1-2). p.70-79
Abstract
While Huntington's disease (HD) is a condition that primarily involves the basal ganglia, there is evidence to suggest that the hypothalamus is also affected. Because the osmoreceptors regulating thirst are situated in the circumventricular region of the hypothalamus, we were interested in whether altered thirst is a part of the HD phenotype. We used the LABORAS behavioural monitoring system and water consumption to show that drinking behaviour was abnormal in R6/2 mice. By 10 weeks of age, R6/2 mice spent significantly more time drinking and drank a greater volume than their wild-type (WT) littermates. The numbers of immunoreactive vasopressin neurons in the paraventricular nucleus (PVN) of the hypothalamus in R6/2 mice were significantly... (More)
While Huntington's disease (HD) is a condition that primarily involves the basal ganglia, there is evidence to suggest that the hypothalamus is also affected. Because the osmoreceptors regulating thirst are situated in the circumventricular region of the hypothalamus, we were interested in whether altered thirst is a part of the HD phenotype. We used the LABORAS behavioural monitoring system and water consumption to show that drinking behaviour was abnormal in R6/2 mice. By 10 weeks of age, R6/2 mice spent significantly more time drinking and drank a greater volume than their wild-type (WT) littermates. The numbers of immunoreactive vasopressin neurons in the paraventricular nucleus (PVN) of the hypothalamus in R6/2 mice were significantly decreased from 8 weeks of age, suggesting that the change in drinking behaviour may be the result of hypothalamic dysfunction. We gave a xerostomia (dry mouth) questionnaire to HD patients and control subjects, and also measured their urine osmolality and serum vasopressin. The mean total xerostomia score was significantly higher in HD patients than in controls, indicating greater thirst in HD patients. Urine osmolality was unaffected in HD patients up to clinical stage 111, and none of the patients had diabetes. However, serum vasopressin was increased, suggesting a dysregulation in the control of hypothalamic vasopressin release. A dry mouth can affect taste, mastication and swallowing, all of which may contribute to the significant weight loss seen in both HD patients and R6/2 mice, as can dehydration. We suggest that increased thirst may be an important and clinically relevant biomarker for the study of disease progression in HD. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
hypothalamus, vasopressin, xerostomia, drinking
in
Brain Research Bulletin
volume
76
issue
1-2
pages
70 - 79
publisher
Elsevier
external identifiers
  • wos:000255577300010
  • scopus:41549091929
ISSN
0361-9230
DOI
10.1016/j.brainresbull.2007.12.007
language
English
LU publication?
yes
id
def389e1-5c05-42ce-a595-eeab1ab8b132 (old id 1204894)
date added to LUP
2008-09-18 11:29:48
date last changed
2017-10-22 03:43:07
@article{def389e1-5c05-42ce-a595-eeab1ab8b132,
  abstract     = {While Huntington's disease (HD) is a condition that primarily involves the basal ganglia, there is evidence to suggest that the hypothalamus is also affected. Because the osmoreceptors regulating thirst are situated in the circumventricular region of the hypothalamus, we were interested in whether altered thirst is a part of the HD phenotype. We used the LABORAS behavioural monitoring system and water consumption to show that drinking behaviour was abnormal in R6/2 mice. By 10 weeks of age, R6/2 mice spent significantly more time drinking and drank a greater volume than their wild-type (WT) littermates. The numbers of immunoreactive vasopressin neurons in the paraventricular nucleus (PVN) of the hypothalamus in R6/2 mice were significantly decreased from 8 weeks of age, suggesting that the change in drinking behaviour may be the result of hypothalamic dysfunction. We gave a xerostomia (dry mouth) questionnaire to HD patients and control subjects, and also measured their urine osmolality and serum vasopressin. The mean total xerostomia score was significantly higher in HD patients than in controls, indicating greater thirst in HD patients. Urine osmolality was unaffected in HD patients up to clinical stage 111, and none of the patients had diabetes. However, serum vasopressin was increased, suggesting a dysregulation in the control of hypothalamic vasopressin release. A dry mouth can affect taste, mastication and swallowing, all of which may contribute to the significant weight loss seen in both HD patients and R6/2 mice, as can dehydration. We suggest that increased thirst may be an important and clinically relevant biomarker for the study of disease progression in HD.},
  author       = {Wood, Nigel I. and Goodman, Anna O. G. and van der Burg, Jorien m and Gazeau, Veronique and Brundin, Patrik and Björkqvist, Maria and Petersen, Asa and Tabrizi, Sarah J. and Barker, Roger A. and Morton, A. Jennifer},
  issn         = {0361-9230},
  keyword      = {hypothalamus,vasopressin,xerostomia,drinking},
  language     = {eng},
  number       = {1-2},
  pages        = {70--79},
  publisher    = {Elsevier},
  series       = {Brain Research Bulletin},
  title        = {Increased thirst and drinking in Huntington's disease and the R6/2 mouse},
  url          = {http://dx.doi.org/10.1016/j.brainresbull.2007.12.007},
  volume       = {76},
  year         = {2008},
}