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.
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.
Authors: R M Chemelli; J T Willie; C M Sinton; J K Elmquist; T Scammell; C Lee; J A Richardson; S C Williams; Y Xiong; Y Kisanuki; T E Fitch; M Nakazato; R E Hammer; C B Saper; M Yanagisawa Journal: Cell Date: 1999-08-20 Impact factor: 41.582
Authors: Tatiana M Korotkova; Olga A Sergeeva; Krister S Eriksson; Helmut L Haas; Ritchie E Brown Journal: J Neurosci Date: 2003-01-01 Impact factor: 6.167
Authors: Jon T Willie; Richard M Chemelli; Christopher M Sinton; Shigeru Tokita; S Clay Williams; Yaz Y Kisanuki; Jacob N Marcus; Charlotte Lee; Joel K Elmquist; Kristi A Kohlmeier; Christopher S Leonard; James A Richardson; Robert E Hammer; Masashi Yanagisawa Journal: Neuron Date: 2003-06-05 Impact factor: 17.173
Authors: Michihiro Mieda; S Clay Williams; Christopher M Sinton; James A Richardson; Takeshi Sakurai; Masashi Yanagisawa Journal: J Neurosci Date: 2004-11-17 Impact factor: 6.167
Authors: Takatoshi Mochizuki; Elda Arrigoni; Jacob N Marcus; Erika L Clark; Mihoko Yamamoto; Michael Honer; Edilio Borroni; Bradford B Lowell; Joel K Elmquist; Thomas E Scammell Journal: Proc Natl Acad Sci U S A Date: 2011-02-28 Impact factor: 11.205
Authors: Kristi A Kohlmeier; Christopher J Tyler; Mike Kalogiannis; Masaru Ishibashi; Morten P Kristensen; Iryna Gumenchuk; Richard M Chemelli; Yaz Y Kisanuki; Masashi Yanagisawa; Christopher S Leonard Journal: Front Neurosci Date: 2013-12-20 Impact factor: 4.677