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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

Bode, Felix J.; Stephan, Michael; Wiehager, Sara; Nguyen, Huu Phuc; Björkqvist, Maria LU ; von Hoersten, Stephan; Bauer, Andreas and Petersén, Åsa LU (2009) In Behavioural Brain Research 205(1). p.175-182
Abstract
Huntington's disease (HID) 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-HT2A- and adrenergic alpha(2)-receptor densities in these regions were significantly... (More)
Huntington's disease (HID) 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-HT2A- 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-HT2A- receptors as therapeutic targets for dysregulation of the circadian activity in HD. (C) 2009 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adrenergic alpha(2)-receptor, forebrain, Basal, Hypothalamus, Sleep, Circadian rhythm, Huntington's disease, Orexin, Leptin
in
Behavioural Brain Research
volume
205
issue
1
pages
175 - 182
publisher
Elsevier
external identifiers
  • wos:000271170700022
  • scopus:70349299834
ISSN
0166-4328
DOI
10.1016/j.bbr.2009.06.031
language
English
LU publication?
yes
id
e194b480-730a-4cb2-85ed-7aeb1569acf7 (old id 1505847)
date added to LUP
2009-11-24 10:29:53
date last changed
2017-07-02 03:28:12
@article{e194b480-730a-4cb2-85ed-7aeb1569acf7,
  abstract     = {Huntington's disease (HID) 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-HT2A- 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-HT2A- receptors as therapeutic targets for dysregulation of the circadian activity in HD. (C) 2009 Elsevier B.V. All rights reserved.},
  author       = {Bode, Felix J. and Stephan, Michael and Wiehager, Sara and Nguyen, Huu Phuc and Björkqvist, Maria and von Hoersten, Stephan and Bauer, Andreas and Petersén, Åsa},
  issn         = {0166-4328},
  keyword      = {Adrenergic alpha(2)-receptor,forebrain,Basal,Hypothalamus,Sleep,Circadian rhythm,Huntington's disease,Orexin,Leptin},
  language     = {eng},
  number       = {1},
  pages        = {175--182},
  publisher    = {Elsevier},
  series       = {Behavioural Brain Research},
  title        = {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},
  url          = {http://dx.doi.org/10.1016/j.bbr.2009.06.031},
  volume       = {205},
  year         = {2009},
}