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http://purl.uniprot.org/citations/19694625http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19694625http://www.w3.org/2000/01/rdf-schema#comment"

Aim

The effect of orexin on wakefulness has been suggested to be largely mediated by activation of histaminergic neurones in the tuberomammillary nucleus (TMN) via orexin receptor-2 (OX(2)R). However, orexin receptors in other regions of the brain might also play important roles in maintenance of wakefulness. To dissect the role of the histaminergic system as a downstream mediator of the orexin system in the regulation of sleep/wake states without compensation by the orexin receptor-1 (OX(1)R) mediated pathways, we analysed the phenotype of Histamine-1 receptor (H(1)R) and OX(1)R double-deficient (H(1)R(-/-);OX(1)R(-/-)) mice. These mice lack OX(1)R-mediated pathways in addition to deficiency of H(1)R, which is thought to be the most important system in downstream of OX(2)R.

Methods

We used H(1)R deficient (H(1)R(-/-)) mice, H(1)R(-/-);OX(1)R(-/-) mice, OX(1)R and OX(2)R double-deficient (OX(1)R(-/-);OX(2)R(-/-)) mice, and wild type controls. Rapid eye movement (REM) sleep, non-REM (NREM) sleep and awake states were determined by polygraphic electroencephalographic/electromyographic recording.

Results

No abnormality in sleep/wake states was observed in H(1)R(-/-) mice, consistent with previous studies. H(1)R(-/-);OX(1)R(-/-) mice also showed a sleep/wake phenotype comparable to that of wild type mice, while OX(1)R(-/-); OX(2)R(-/-) mice showed severe fragmentation of sleep/wake states.

Conclusion

Our observations showed that regulation of the sleep/wake states is completely achieved by OX(2)R-expressing neurones without involving H(1)R-mediated pathways. The maintenance of basal physiological sleep/wake states is fully achieved without both H(1) and OX(1) receptors. Downstream pathways of OX(2)R other than the histaminergic system might play an important role in the maintenance of sleep/wake states."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.org/dc/terms/identifier"doi:10.1111/j.1748-1716.2009.02032.x"xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Nagai K."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Sakurai T."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Watanabe T."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Yanagisawa M."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Ohno K."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Willie J.T."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Hondo M."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/author"Kisanuki Y."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/name"Acta Physiol (Oxf)"xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/pages"287-294"xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/title"Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintenance of basal sleep/wake states."xsd:string
http://purl.uniprot.org/citations/19694625http://purl.uniprot.org/core/volume"198"xsd:string
http://purl.uniprot.org/citations/19694625http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19694625
http://purl.uniprot.org/citations/19694625http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19694625
http://purl.uniprot.org/uniprot/#_Q0VDP6-mappedCitation-19694625http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19694625
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http://purl.uniprot.org/uniprot/#_B3Y5T0-mappedCitation-19694625http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19694625
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http://purl.uniprot.org/uniprot/#_P58307-mappedCitation-19694625http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19694625
http://purl.uniprot.org/uniprot/#_P58308-mappedCitation-19694625http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19694625
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