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Increased numbers of motor activity peaks during light cycle are associated with reductions in adrenergic alpha(2)-receptor levels in a transgenic Huntington's disease rat model.

Authors: Bode, FJ  Stephan, M  Wiehager, S  Nguyen, HP  Bjorkqvist, M  Von Horsten, S  Bauer, A  Petersen, A 
Citation: Bode FJ, etal., Behav Brain Res. 2009 Dec 14;205(1):175-82. Epub 2009 Jun 30.
Pubmed: (View Article at PubMed) PMID:19573560
DOI: Full-text: DOI:10.1016/j.bbr.2009.06.031

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. Besides psychiatric, motor and cognitive symptoms, HD patients suffer from sleep disturbances. In order to screen a rat model transgenic for HD (tgHD rats) for sleep-wake cycle dysregulation, we monitored their circadian activity peaks in the present study. TgHD rats of both sexes showed hyperactivity during the dark cycle and more frequent light cycle activity peaks indicative for a disturbed sleep-wake cycle. Focusing on males at the age of 4 and 14 months, analyses of receptor levels in the hypothalamus and the basal forebrain revealed that 5-HT(2A)- and adrenergic alpha(2)-receptor densities in these regions were significantly altered in tgHD rats compared to their wild-type littermates. Adrenergic receptor densities correlated negatively with the light cycle hyperactivity peaks at later stages of the disease in male tgHD rats. Furthermore, reduced leptin levels, a feature associated with circadian misalignment, were present. Our study demonstrates that the male tgHD rat is a suitable model to investigate HD associated sleep alterations. Further studies are warranted to elucidate the role of adrenergic- and 5-HT(2A)-receptors as therapeutic targets for dysregulation of the circadian activity in HD.

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RGD Object Information
RGD ID: 5128676
Created: 2011-03-15
Species: All species
Last Modified: 2011-03-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.