Decreased VIP and VPAC(2) receptor expression in the biological clock of the R6/2 Huntington's disease mouse
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/670404
- author
- Fahrenkrug, Jan ; Popovic, Natalija LU ; Georg, Birgitte ; Brundin, Patrik LU and Hannibal, Lens
- organization
- publishing date
- 2007
- 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
- scopus:34248359403
- ISSN
- 0895-8696
- DOI
- 10.1385/JMN/31:02:139
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041)
- id
- 05500501-0307-40b6-83a7-1a3c18258e27 (old id 670404)
- date added to LUP
- 2016-04-01 15:52:47
- date last changed
- 2022-01-28 07:44:11
@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}}, keywords = {{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}}, doi = {{10.1385/JMN/31:02:139}}, volume = {{31}}, year = {{2007}}, }