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

每日限食（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（orexin，GIP）是一种在睡眠-觉醒调节和摄食行为调节中起重要作用的神经肽，可能参与了射频诱导节律的产生。在维持12 h光/暗循环的小鼠中，下丘脑外侧部的前食欲素原mRNA和食欲素A蛋白水平在AD下没有表现出每日变化，但食欲素神经元中的Fos表达在夜间高，如先前报道的。9天的日间RF产生预期的每日运动活动，并将mDbp mRNA节律的清晨峰值转移到大脑皮层和尾壳核中的傍晚峰值。在此条件下，食欲素的表达在mRNA和蛋白水平上没有改变。而RF处理小鼠的食欲素神经元Fos表达在白天较高。另一方面，两个食欲素受体的表达没有显示出每日的变化在随意和RF条件下。结合前人的工作，本研究结果表明，下丘脑外侧区食欲素神经元的活性参与了行为活动和摄食行为的促进和维持。

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.