Article

Increased metabolism in the R6/2 mouse model of Huntington’s disease

Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University BMC A10, Lund, Sweden; Unit of Molecular Metabolism, Department of Experimental Medical Science, CRC 91-11, Malmo, Sweden; Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK; Unit of Appetite Control, Department of Experimental Medical Science, BMC F13, Lund, Sweden; Unit of Neuroendocrine Cell Biology, Department of Experimental Medical Science, BMC B11, Lund, Sweden; Neuroscience Division, Yerkes Primate Center of Emory University, Atlanta GA, USA; Department of Medical and Molecular Genetics, GKT School of Medicine, King’s College, Guy’s Hospital, London, UK; Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, BMC B11, Lund, Sweden
Neurobiology of Disease DOI:10.1016/j.nbd.2007.07.029 pp.41-51

ABSTRACT Huntington’s disease (HD) is a hereditary disorder characterized by personality changes, chorea, dementia and weight loss. The cause of this weight loss is unknown. The aim of this study was to examine body weight changes and weight-regulating factors in HD using the R6/2 mouse model as a tool. We found that R6/2 mice started losing weight at 9 weeks of age. Total locomotor activity was unaltered and caloric intake was not decreased until 11 weeks of age, which led us to hypothesize that increased metabolism might underlie the weight loss. Indeed, oxygen consumption in R6/2 mice was elevated from 6 weeks of age, indicative of an increased metabolism. Several organ systems that regulate weight and metabolism, including the hypothalamus, the stomach and adipose tissue displayed abnormalities in R6/2 mice. Together, these data demonstrate that weight loss in R6/2 mice is associated with increased metabolism and changes in several weight-regulating factors.

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Keywords

6 weeks
 
9 weeks
 
adipose tissue
 
body weight changes
 
dementia
 
hereditary disorder
 
Huntington’s disease
 
hypothalamus
 
increased metabolism
 
metabolism
 
organ systems
 
oxygen consumption
 
personality changes
 
R6/2 mouse model
 
regulate weight
 
Total locomotor activity
 
weight loss
 
weight-regulating factors