CO2 activates orexin-containing neurons in mice.
Accumulating evidence shows possible participation of orexin, a hypothalamic neuropeptide also known as hypocretin, in regulation of breathing. In this study we examined whether hypercapnic stimulation in vivo activates orexin-containing neurons in the hypothalamus. A hypercapnic gas mixture of 10% CO(2), 21% O(2), and residual N(2) or room air was inhaled to awake and freely moving mice for 3h. Their brains were examined by double immunohistochemical staining for orexin and c-Fos. We found that inhalation of CO(2) significantly increased c-Fos expression in the orexin-containing cells that were located in the perifornical region and the dorsomedial hypothalamus (15.8+/-1.6% for room air vs. 28.4+/-2.7% for CO(2), p=0.011) but not in the lateral hypothalamic area (12.3+/-1.2% for room air vs. 12.4+/-3.0% for CO(2)). Although current methodology cannot differentiate between direct effect of CO(2) on the orexin-containing neurons and indirect one through other neurons, this is the first report showing that inhalation of CO(2) did activate the orexin-containing neurons in vivo.
Sunanaga
Jinko
J
Department of Physiology, Kagoshima University Graduate School of Medical & Dental Sciences, Kagoshima 890-8544, Japan. jinko@m2.kufm.kagoshima-u.ac.jp
Deng
Ben-Shiang
BS
Zhang
Wei
W
Kanmura
Yuichi
Y
Kuwaki
Tomoyuki
T
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology*; D002452:Cell Count; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D002245:Carbon Dioxide