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Decreased VIP and V...
Decreased VIP and VPAC(2) receptor expression in the biological clock of the R6/2 Huntington's disease mouse
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Fahrenkrug, Jan (author)
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- Popovic, Natalija (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Georg, Birgitte (author)
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- Brundin, Patrik (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Hannibal, Lens (author)
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: Journal of Molecular Neuroscience. - 0895-8696. ; 31:2, s. 139-148
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- suprachiasmatic nucleus
- circadian rhythm
- Huntington's disease
- vasoactive intestinal polypeptide
Publication and Content Type
- art (subject category)
- ref (subject category)
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