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Decreased VIP and VPAC(2) receptor expression in the biological clock of the R6/2 Huntington's disease mouse

Fahrenkrug, Jan; Popovic, Natalija LU ; Georg, Birgitte; Brundin, Patrik LU and Hannibal, Lens (2007) In Journal of Molecular Neuroscience 31(2). p.139-148
Abstract
Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG triplet repeat expansion in the gene encoding the protein huntingtin. The most studied model of HD, the R6/2 transgenic mouse, replicates many features of the disease. In addition to motor, cognitive, and endocrine dysfunctions, these mice exhibit a progressive disruption of circadian rhythms. This is accompanied by an altered expression of the circadian clock genes in the suprachiasmatic nucleus/nuclei (SCN), the principal circadian pacemaker in the brain. The neuropeptide vasoactive intestinal polypeptide (VIP) and its receptor VPAC(2) are highly expressed in the SCN, and VIPergic signaling plays an essential role in maintenance of ongoing circadian... (More)
Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG triplet repeat expansion in the gene encoding the protein huntingtin. The most studied model of HD, the R6/2 transgenic mouse, replicates many features of the disease. In addition to motor, cognitive, and endocrine dysfunctions, these mice exhibit a progressive disruption of circadian rhythms. This is accompanied by an altered expression of the circadian clock genes in the suprachiasmatic nucleus/nuclei (SCN), the principal circadian pacemaker in the brain. The neuropeptide vasoactive intestinal polypeptide (VIP) and its receptor VPAC(2) are highly expressed in the SCN, and VIPergic signaling plays an essential role in maintenance of ongoing circadian rhythmicity. We found a marked reduction in both VIP mRNA and VPAC2 receptor mRNA, quantified by RT-PCR, as well as a decrease in VIP immunostaining in the SCN of R6/2 mice. These changes were coupled to a disruption of circadian rhythm. We observed no loss of neurons in the SCN and therefore suggest that the changes in VIP and VPAC2 receptor are due to their decreased expression. In conclusion, we propose that impaired VIPergic signaling is an additional candidate mechanism for disruption of circadian rhythms in R6/2 mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
suprachiasmatic nucleus, circadian rhythm, Huntington's disease, vasoactive intestinal polypeptide
in
Journal of Molecular Neuroscience
volume
31
issue
2
pages
139 - 148
publisher
Humana Press
external identifiers
  • wos:000244800300005
ISSN
0895-8696
DOI
10.1385/JMN/31:02:139
language
English
LU publication?
yes
id
05500501-0307-40b6-83a7-1a3c18258e27 (old id 670404)
date added to LUP
2007-12-10 09:41:16
date last changed
2016-04-16 03:29:06
@article{05500501-0307-40b6-83a7-1a3c18258e27,
  abstract     = {Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG triplet repeat expansion in the gene encoding the protein huntingtin. The most studied model of HD, the R6/2 transgenic mouse, replicates many features of the disease. In addition to motor, cognitive, and endocrine dysfunctions, these mice exhibit a progressive disruption of circadian rhythms. This is accompanied by an altered expression of the circadian clock genes in the suprachiasmatic nucleus/nuclei (SCN), the principal circadian pacemaker in the brain. The neuropeptide vasoactive intestinal polypeptide (VIP) and its receptor VPAC(2) are highly expressed in the SCN, and VIPergic signaling plays an essential role in maintenance of ongoing circadian rhythmicity. We found a marked reduction in both VIP mRNA and VPAC2 receptor mRNA, quantified by RT-PCR, as well as a decrease in VIP immunostaining in the SCN of R6/2 mice. These changes were coupled to a disruption of circadian rhythm. We observed no loss of neurons in the SCN and therefore suggest that the changes in VIP and VPAC2 receptor are due to their decreased expression. In conclusion, we propose that impaired VIPergic signaling is an additional candidate mechanism for disruption of circadian rhythms in R6/2 mice.},
  author       = {Fahrenkrug, Jan and Popovic, Natalija and Georg, Birgitte and Brundin, Patrik and Hannibal, Lens},
  issn         = {0895-8696},
  keyword      = {suprachiasmatic nucleus,circadian rhythm,Huntington's disease,vasoactive intestinal polypeptide},
  language     = {eng},
  number       = {2},
  pages        = {139--148},
  publisher    = {Humana Press},
  series       = {Journal of Molecular Neuroscience},
  title        = {Decreased VIP and VPAC(2) receptor expression in the biological clock of the R6/2 Huntington's disease mouse},
  url          = {http://dx.doi.org/10.1385/JMN/31:02:139},
  volume       = {31},
  year         = {2007},
}