Wake-promoting effects of orexin: Its independent actions against the background of an impaired corticotropine-releasing hormone receptor system
Wake-promoting effects of orexin: Its independent actions against the background of an impaired corticotropine-releasing hormone receptor system
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DOI：
10.1016/j.bbr.2011.03.026
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发表时间：
2011-09-12
影响因子：
2.7
通讯作者：
Kimura, Mayumi
中科院分区：
文献类型：
--
作者：
Fenzl, Thomas;Romanowski, Christoph P. N.;Kimura, Mayumi
人们普遍认为食欲素（下丘脑促分泌素）具有促进睡眠的作用。在正常情况下，食欲素释放的昼夜节律具有明显的昼夜节律分布，而在抑郁症中，食欲素波动的幅度受到抑制。有趣的是，抑郁症的临床症状包括几种睡眠障碍。在这种疾病中，促肾上腺皮质激素释放激素（CRH）似乎是影响睡眠的另一个因素。由于食欲素和CRH系统之间的神经生理相互作用和解剖学联系表明这两种神经肽相互影响，我们研究了两种不同的CRH受体敲除模型中功能失调的CRH受体系统是否会改变外源性食欲素的一般促醒作用。将Orexin注入cns限制性crh -受体1型敲除小鼠（CRH-R1 KO）和crh -受体2型敲除小鼠（CRH-R2 KO）的脑室内，记录自由行为小鼠的基线睡眠。第三个实验是在CRH-R1 KO动物体内注射抗索瓦菌素-30 （CRH-R2拮抗剂）。Orexin在CRH-R1 KO小鼠、CRH-R2 KO动物和抗sauvagine-30处理的CRH-R1 KO小鼠中具有相似的促醒作用。所有相应的对照窝友实验结果一致。根据我们的结果，我们得出结论，促醒作用的食欲素不受可能的贡献CRH的影响。(C) 2011 Elsevier B.V.版权所有
It is widely accepted that orexin (hypocretin) bears wake-promoting effects. While under normal conditions the circadian rhythm of orexin release has a clear circadian distribution, the amplitude of orexin fluctuation is dampened in depression. Interestingly, clinical symptoms of depression include several sleep disturbances. In this disease, corticotropin-releasing hormone (CRH) seems to be another factor influencing sleep. As neurophysiological interactions and anatomical connections between the orexinergic and the CRH system point to mutual influences of these two neuropeptides, we examined whether a dysfunctional CRH-receptor system in two different CRH receptor knock out models alters general wake-promoting effects of orexin applied exogenously.Orexin was injected intracerebroventricularlly into CNS-restricted CRH-receptor type 1 knockout mice (CRH-R1 KO) and CRH-receptor type 2 knockout mice (CRH-R2 KO) and baseline sleep was recorded from the freely behaving mice. A third experiment included antisauvagine-30 injections (CRH-R2 antagonist) into CRH-R1 KO animals. Orexin had similar wake-promoting effects in CRH-R1 KO mice, in CRH-R2 KO animals and in CRH-R1 KO mice treated with antisauvagine-30. Consistent results were obtained from all corresponding control littermate experiments. According to our results we conclude that the wake-promoting effects of orexin are not influenced by a possible contribution of CRH. (C) 2011 Elsevier B.V. All rights reserved.