Research on molecular mechanism of sleep-wakefulness rhythm and development of new hypnotics

睡眠-觉醒节律分子机制研究及新型安眠药开发

基本信息

批准号：
13470016
负责人：
SHIBATA Shigenobu
金额：
$ 9.09万
依托单位：
Waseda University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470016/
关键词：
Circadian Clock gene Orexin Sleep feeding behavior anticipation lateral hypothalamus biological clock 概日リズム睡眠薬

项目摘要

Daily restricted feeding (RF) can produce anticipatory rhythms at both locomotor activity and molecular oscillator level. As orexin Giypocretin) is a neuropeptide playing a critical role in the regulation of both sleep-wake regulation and feeding behavior orexin might be participated in the generation of RF-induced rhythm. In mouse maintained on a 12 h light/dark cycle, preproorexin mRNA and Orexin A protein level in the lateral hypothalamus did not show daily variations under ad loitum but Fos expression in the orexin neurons are high in the night as previously reported. 9 days of daytime RF generated anticipatory daily locomotor activity and shifted the early morning peak of mDbp mRNA rhythm changed to a late evening peak in the cerebral cortex and Caudate putamen. Under these conditions, orexin expression was not changed at mRNA and protein level. However, Fos expression in orexin neuron was higher in the daytime in RF treated mice. On the other hand, expression of two orexin receptors did not show daily variation under ad libitum and RF conditions. In combination of previous work, present results suggest that activity of orexin neuron in the lateral hypothalamus contributes the promotion and maintenance of behavioral activity and feeding behavior.

每日限制进食（RF）可以在运动活动和分子振荡器水平上产生预期节律。食欲素（Gypocretin）是一种神经肽，在睡眠-觉醒调节和进食行为的调节中发挥着关键作用，食欲素可能参与射频诱导节律的产生。在维持 12 小时光/暗周期的小鼠中，外侧下丘脑中的前食欲素原 mRNA 和食欲素 A 蛋白水平在闲置状态下没有表现出每日变化，但如先前报道的，食欲素神经元中的 Fos 表达在夜间很高。 9 天的日间 RF 产生了预期的日常运动活动，并将 mDbp mRNA 节律的清晨峰值转变为大脑皮层和尾壳核中的傍晚峰值。在这些条件下，食欲素表达在 mRNA 和蛋白质水平上没有变化。然而，RF 治疗的小鼠白天食欲素神经元中的 Fos 表达较高。另一方面，两种食欲素受体的表达在随意和RF条件下没有表现出每日变化。结合之前的工作，目前的结果表明，下丘脑外侧的食欲素神经元的活动有助于行为活动和摄食行为的促进和维持。