title: Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.
abstract: Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent.
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan; Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan; Department of Anesthesiology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki 569-8686, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan; Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Futatsuki
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Ushikai
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan; Department of Anesthesiology and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kuroki
authors.affiliation: Department of Anesthesiology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki 569-8686, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Minami
authors.affiliation: Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kakihana
authors.affiliation: Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan. Electronic address: kuwaki@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwaki
mesh_terms: D000818:Animals; D001049:Apnea / Q000139:chemically induced / Q000150:complications; D002245:Carbon Dioxide / Q000009:adverse effects; D002452:Cell Count; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D007031:Hypothalamus / Q000473:pathology*; D000860:Hypoxia / Q000209:etiology / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013997:Time Factors
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D002245:Carbon Dioxide
keywords: Hypocretin; Hypothalamus; Hypoxia; Sleep apnea; c-Fos