| 1. |
- Fahrenkrug, Jan, et al.
(författare)
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Decreased VIP and VPAC(2) receptor expression in the biological clock of the R6/2 Huntington's disease mouse
- 2007
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Ingår i: Journal of Molecular Neuroscience. - 0895-8696. ; 31:2, s. 139-148
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Liu, Xiaobin, et al.
(författare)
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Molecular Fingerprint of Neuropeptide S-Producing Neurons in the Mouse Brain
- 2011
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Ingår i: JOURNAL OF COMPARATIVE NEUROLOGY. - : John Wiley and Sons, Ltd. - 0021-9967. ; 519:10, s. 1847-1866
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide S (NPS) has been associated with a number of complex brain functions, including anxiety-like behaviors, arousal, sleep-wakefulness regulation, drug-seeking behaviors, and learning and memory. In order to better understand how NPS influences these functions in a neuronal network context, it is critical to identify transmitter systems that control NPS release and transmitters that are co-released with NPS. For this purpose, we generated several lines of transgenic mice that express enhanced green-fluorescent protein (EGFP) under control of the endogenous NPS precursor promoter. NPS/EGFP-transgenic mice show anatomically correct and overlapping expression of both NPS and EGFP. A total number of similar to 500 NPS/EGFP-positive neurons are present in the mouse brain, located in the pericoerulear region and the Kolliker-Fuse nucleus. NPS and transgene expression is first detectable around E14, indicating a potential role for NPS in brain development. EGFP-positive cells were harvested by laser-capture microdissection, and mRNA was extracted for expression profiling by using microarray analysis. NPS was found co-localized with galanin in the Kolliker-Fuse nucleus of the lateral parabrachial area. A dense network of orexin/hypocretin neuronal projections contacting pericoerulear NPS-producing neurons was observed by immunostaining. Expression of a distinct repertoire of metabotropic and ionotropic receptor genes was identified in both NPS neuronal clusters that will allow for detailed investigations of incoming neurotransmission, controlling neuronal activity of NPS-producing neurons. Stress-induced functional activation of NPS-producing neurons was detected by staining for the immediate-early gene c-fos, thus supporting earlier findings that NPS might be part of the brain stress response network.
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| 3. |
- Nilsson, Christer, et al.
(författare)
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Epithelial cells purified from choroid plexus have receptors for vasoactive intestinal polypeptide
- 1991
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Ingår i: Brain Research. - 1872-6240. ; 542:2, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- Using the choroid plexus from pig a method has been developed to purify the epithelial cells from the underlying vascularized connective tissue stroma. An epithelial cell fraction was obtained that showed a purity of at least 95%, as determined by light microscopic analysis. The epithelial cells were investigated for the presence of binding sites for the neurotransmitter peptide, vasoactive intestinal polypeptide (VIP). Suspensions of epithelial cells were found to have high affinity binding sites for 125I-labelled VIP, with maximum binding obtained after 30 min incubation at 20 degrees C with a concentration of 50 micrograms cell protein per sample. Competition experiments with displacement of [125I]VIP binding by increasing concentrations of unlabeled VIP indicated the presence of a single class of binding sites with a Kd of 3 nM and a binding capacity of 970 pmol/g cell protein. Cross-linking of [125I]VIP to epithelial cells with disuccinimido dithiobis (propionate) (DSP), followed by SDS-polyacrylamide gel electrophoresis, demonstrated binding to a single 55 kD protein. The receptor was highly specific for VIP as binding was only inhibited in the presence of high concentrations of the related peptides helodermin, growth hormone-releasing factor, secretin, and peptide histidine isoleucine. This is the first demonstration of VIP-binding to choroid plexus epithelial cells.
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| 4. |
- Vrang, Niels, et al.
(författare)
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The Imprinted Gene Neuronatin Is Regulated by Metabolic Status and Associated With Obesity.
- 2010
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 18:7, s. 1289-1296
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Tidskriftsartikel (refereegranskat)abstract
- Using restriction fragment differential display (RFDD) technology, we have identified the imprinted gene neuronatin (Nnat) as a hypothalamic target under the influence of leptin. Nnat mRNA expression is decreased in several key appetite regulatory hypothalamic nuclei in rodents with impaired leptin signaling and during fasting conditions. Furthermore, peripheral administration of leptin to ob/ob mice normalizes hypothalamic Nnat expression. Comparative immunohistochemical analysis of human and rat hypothalami demonstrates that NNAT protein is present in anatomically equivalent nuclei, suggesting human physiological relevance of the gene product(s). A putative role of Nnat in human energy homeostasis is further emphasized by a consistent association between single nucleotide polymorphisms (SNPs) in the human Nnat gene and severe childhood and adult obesity.
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