Zhang Shengwen, Zeitzer Jamie M, Yoshida Yasushi, Wisor Jonathan P, Nishino Seiji, Edgar Dale M, Mignot Emmanuel
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
Sleep. 2004 Jun 15;27(4):619-27. doi: 10.1093/sleep/27.4.619.
Hypocretins (orexins) are involved in the sleep disorder narcolepsy. While hypocretin-1 has a daily oscillation, little is known regarding the relative contribution of circadian and homeostatic components on hypocretin release. The effect of lesions of the suprachiasmatic nucleus (SCN) on hypocretin-1 in the cerebrospinal fluid (CSF) was examined.
SCN-ablated (SCNx) and sham-operated control rats were implanted with activity-temperature transmitters. Animals were housed individually under 1 of 3 lighting conditions: 12-hour:12-hour light:dark cycle (LD), constant light (LL), and constant darkness (DD). Lesions were verified histologically and shown not to affect hypocretin-containing cells. Hypocretin-1 concentrations in the CSF were determined every 4 hours using radioimmunoassays.
Control animals displayed robust circadian (LL, DD) and diurnal (LD) fluctuations in CSF hypocretin-1, locomotor activity, and temperature. Peak CSF hypocretin-1 was at the end of the active period. Activity, temperature, and CSF hypocretin-1 were arrhythmic in SCNx animals in LL and DD. In LD, a weak but significant fluctuation in activity and temperature but not CSF hypocretin-1 was observed in SCNx animals. We also explored correlations between CSF hypocretin-1, CSF corticosterone, and locomotor activity occurring prior to CSF sampling in arrhythmic SCNx rats under constant conditions. Significant correlations between hypocretin-1 and activity were observed both across and within animals, suggesting that interindividual and time-of-the-day differences in activity have significant effects on hypocretin release in arrhythmic animals. No correlation was found between CSF hypocretin-1 and corticosterone.
Hypocretin-1 release is under SCN control. Locomotor activity influences the activity of the hypocretin neurons.
下丘脑分泌素（食欲素）与发作性睡病这一睡眠障碍有关。虽然下丘脑分泌素-1具有每日节律性波动，但关于昼夜节律和稳态成分对下丘脑分泌素释放的相对贡献，人们了解甚少。本研究检测了损毁视交叉上核（SCN）对脑脊液（CSF）中下丘脑分泌素-1的影响。
对损毁SCN（SCNx）的大鼠和假手术对照大鼠植入活动-温度发射器。将动物分别饲养在三种光照条件之一：12小时光照：12小时黑暗循环（LD）、持续光照（LL）和持续黑暗（DD）。通过组织学验证损伤情况，并显示其不影响含下丘脑分泌素的细胞。每4小时使用放射免疫分析法测定CSF中的下丘脑分泌素-1浓度。
对照动物的CSF下丘脑分泌素-1、运动活动和体温呈现出强烈的昼夜节律（LL、DD）和日节律（LD）波动。CSF下丘脑分泌素-1的峰值出现在活动期结束时。在LL和DD条件下，SCNx动物的活动、体温和CSF下丘脑分泌素-1均无节律。在LD条件下，SCNx动物的活动和体温有微弱但显著的波动，而CSF下丘脑分泌素-1没有。我们还探讨了在恒定条件下无节律的SCNx大鼠CSF采样前，CSF下丘脑分泌素-1、CSF皮质酮和运动活动之间的相关性。在动物之间和动物体内均观察到下丘脑分泌素-1与活动之间存在显著相关性，这表明活动的个体间差异和一天中的时间差异对无节律动物的下丘脑分泌素释放有显著影响。未发现CSF下丘脑分泌素-1与皮质酮之间存在相关性。
下丘脑分泌素-1的释放受SCN控制。运动活动会影响下丘脑分泌素神经元的活性。
