Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice
Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice
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DOI：
10.1152/japplphysiol.00679.2006
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Kuwaki, Tomoyuki
中科院分区：
文献类型：
--
作者：
Nakamura, Akira;Zhang, Wei;Kuwaki, Tomoyuki
外源性施用食欲素可以促进觉醒和呼吸。在这里，我们检查了内在食欲素是否以警觉状态依赖的方式参与呼吸控制。白天，前食欲素基因敲除小鼠 (ORX-KO) 和野生型 (WT) 同窝小鼠的通气情况与脑电图和肌电图一起记录 6 小时。在安静清醒（QW）、慢波睡眠（SWS）或快速眼动（REM）睡眠期间分别测定呼吸参数。无论警惕状态如何，ORX-KO 的基础通气量均正常。 ORX-KO 中 QW 期间的高碳酸通气反应 (0.19 +/- 0.01 ml . min(-1) . g(-1) .% CO2-1) 显着小于 WT 小鼠 (0.38 +/- 0.04 ml . min(-1) . g(-1) .% CO2-1)，而 ORX-KO 中 SWS 和 REM 期间的反应与WT小鼠。不同基因型在清醒和睡眠期间的缺氧反应没有差异。在 SWS 和 REM 睡眠期间，ORX-KO 中自发性而非叹息后睡眠呼吸暂停比 WT 同窝小鼠更常见。我们的研究结果表明，食欲素在清醒期间的二氧化碳敏感性和睡眠期间保持通气稳定性方面发挥着至关重要的作用。
Exogenous administration of orexin can promote wakefulness and respiration. Here we examined whether intrinsic orexin participates in the control of breathing in a vigilance state-dependent manner. Ventilation was recorded together with electroencephalography and electromyography for 6 h during the daytime in prepro-orexin knockout mice ( ORX-KO) and wild-type ( WT) littermates. Respiratory parameters were separately determined during quiet wakefulness ( QW), slow-wave sleep ( SWS), or rapid eye movement ( REM) sleep. Basal ventilation was normal in ORX-KO, irrespective of vigilance states. The hypercapnic ventilatory response during QW in ORX-KO ( 0.19 +/- 0.01 ml . min(-1) . g(-1) .% CO2-1) was significantly smaller than that in WT mice ( 0.38 +/- 0.04 ml . min(-1) . g(-1) .% CO2-1), whereas the responses during SWS and REM in ORX-KO were comparable to those in WT mice. Hypoxic responses during wake and sleep periods were not different between the genotypes. Spontaneous but not postsigh sleep apneas were more frequent in ORX-KO than in WT littermates during both SWS and REM sleep. Our findings suggest that orexin plays a crucial role both in CO2 sensitivity during wakefulness and in preserving ventilation stability during sleep.