Intermittent but not sustained hypoxia activates orexin-containing neurons in mice

Respir Physiol Neurobiol. 2015 Jan 15;206:11-4. doi: 10.1016/j.resp.2014.11.003. Epub 2014 Nov 11.


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.

Keywords: Hypocretin; Hypothalamus; Hypoxia; Sleep apnea; c-Fos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apnea / chemically induced
  • Apnea / complications
  • Carbon Dioxide / adverse effects
  • Cell Count
  • Disease Models, Animal
  • Gene Expression Regulation / physiology
  • Hypothalamus / pathology*
  • Hypoxia / etiology
  • Hypoxia / pathology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Orexins
  • Proto-Oncogene Proteins c-fos / metabolism
  • Time Factors


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Proto-Oncogene Proteins c-fos
  • Carbon Dioxide