Division of Physiology and Biocenter of Oulu, Department of Biomedicine, University of Oulu, Oulu, Finland.
Acta Physiol (Oxf). 2010 Mar;198(3):237-49. doi: 10.1111/j.1748-1716.2009.02068.x. Epub 2009 Dec 10.
Orexin/hypocretin peptides are expressed in the lateral hypothalamus and involved in the regulation of autonomic functions, energy homeostasis and arousal states. The sleep disorder narcolepsy, which is characterized by excessive daytime sleepiness and occurrence of sudden rapid eye movement (REM) sleep, is associated with a loss of orexin neurones. Our study investigated the effects of orexins on sleep-wake patterns in a novel transgenic mouse line overexpressing the human prepro-orexin (hPPO) gene under the control of its endogenous promoter.
Orexin overexpression was investigated by PCR, Southern and Western blotting as well as immunohistochemistry. Polysomnographic recordings were performed for analyses of sleep-wake patterns and for electroencephalographic activity during 24 h baseline and during and after 6 h of sleep deprivation (SD).
Transgenic hPPO mice had increased expression of human prepro-orexin (hPPO) and orexin-A in the hypothalamus. Transgene expression decreased endogenous orexin-2 receptors but not orexin-1 receptors in the hypothalamus without affecting orexin receptor levels in the basal forebrain, cortex or hippocampus. Transgenic mice compared with their wild type littermates showed small but significant differences in the amount of waking and slow wave sleep, particularly during the light-dark transition periods, in addition to a slight reduction in REM sleep during baseline and during recovery sleep after SD.
The hPPO-overexpressing mice show a small reduction in REM sleep, in addition to differences in vigilance state amounts in the light/dark transition periods, but overall the sleep-wake patterns of hPPO-overexpressing mice do not significantly differ from their wild type littermates.
食欲素/下丘脑泌素肽在外侧下丘脑表达，参与自主功能、能量平衡和觉醒状态的调节。以白天过度嗜睡和快速眼动（REM）睡眠突然发作为特征的睡眠障碍——发作性睡病与食欲素神经元缺失有关。我们的研究通过过表达人前脑啡肽原（hPPO）基因的新型转基因小鼠系（该基因在其内源性启动子的控制下表达），调查了食欲素对睡眠-觉醒模式的影响。
通过 PCR、Southern 和 Western 印迹以及免疫组织化学研究了食欲素的过表达。进行多导睡眠记录，以分析睡眠-觉醒模式，并在 24 小时基线以及睡眠剥夺（SD）期间和之后 6 小时期间分析脑电图活动。
转基因 hPPO 小鼠下丘脑中人前脑啡肽原（hPPO）和食欲素-A 的表达增加。转基因表达降低了下丘脑内的内源性食欲素-2 受体，但不影响基底前脑、皮质或海马中的食欲素受体水平。与野生型同窝仔相比，转基因小鼠在清醒和慢波睡眠的量上表现出微小但显著的差异，尤其是在光-暗转换期间，此外，在基线期间和 SD 后恢复睡眠期间，REM 睡眠也略有减少。
hPPO 过表达小鼠的 REM 睡眠略有减少，此外，在光/暗转换期间警觉状态量的差异，但总体而言，hPPO 过表达小鼠的睡眠-觉醒模式与野生型同窝仔没有显著差异。
