Onoe H, Watanabe Y, Ono K, Koyama Y, Hayaishi O
Department of Neuroscience, Osaka Bioscience Institute, Japan.
J Neurosci. 1992 Jul;12(7):2715-25. doi: 10.1523/JNEUROSCI.12-07-02715.1992.
The precise sites for prostaglandin E2 (PGE2)-related activity responsible for the promotion of wakefulness and elevation of brain temperature were determined in several regions of the monkey brain. PGE2 was administered through a microdialysis probe into 11 brain loci mainly in the preoptic area/anterior hypothalamic region (POA/AH) and the tuberomammillary region in the posterior hypothalamus (TuM-PH). Administration of PGE2 into the POA/AH resulted in a marked and dose-dependent febrile response. When a low dose (15 pmol/min) of PGE2 was administered into the POA/AH, brain temperature increased significantly up to a 0.6 degrees C rise, but sleep behavior and amounts of time in wakefulness, slow wave sleep (SWS), and REM sleep during the administration period were not significantly different from those of the control monkeys. Dose of PGE2 above 150 pmol/min elevated the brain temperature and heart rate more markedly and suppressed sleep. The degree of inhibition of sleep by PGE2 was closely correlated with the changes in these autonomic responses. On the other hand, when a low dose of PGE2 was administered into the TuM-PH, the time spent awake during the administration period increased up to 3.5-fold and the amount of time spent in SWS decreased to 50% of that of the control level, with negligible changes in brain temperature and heart rate. The awaking response of PGE2 in the TuM-PH was also dose dependent, but was not correlated with the change in brain temperature. Among 11 brain regions tested, the hyperthermic effect of PGE2 was most potent in the POA, while its awaking effect was most pronounced in the TuM-PH close to the mammillary complex. These findings demonstrate that the site of action of PGE2 for the regulation of sleep-wakefulness is clearly distinct from that for the temperature regulation. PGE2 may be involved in the neurochemical mechanism of wakefulness mediated in a specific site in the PH.
在猴脑的几个区域中确定了负责促进清醒和提高脑温的前列腺素E2（PGE2）相关活性的确切位点。通过微透析探针将PGE2注入11个脑位点，主要位于视前区/下丘脑前部区域（POA/AH）和下丘脑后部的乳头体区域（TuM-PH）。将PGE2注入POA/AH会导致明显的剂量依赖性发热反应。当向POA/AH注入低剂量（15 pmol/分钟）的PGE2时，脑温显著升高，最高升高0.6摄氏度，但给药期间的睡眠行为以及清醒、慢波睡眠（SWS）和快速眼动睡眠的时间与对照猴相比无显著差异。PGE2剂量高于150 pmol/分钟时，脑温和心率升高更明显，且抑制睡眠。PGE2对睡眠的抑制程度与这些自主反应的变化密切相关。另一方面，当向TuM-PH注入低剂量的PGE2时，给药期间的清醒时间增加至3.5倍，SWS时间减少至对照水平的50%，脑温和心率变化可忽略不计。PGE2在TuM-PH中的唤醒反应也是剂量依赖性的，但与脑温变化无关。在测试的11个脑区中，PGE2的热效应在POA中最强，而其唤醒效应在靠近乳头体复合体的TuM-PH中最明显。这些发现表明，PGE2调节睡眠-清醒的作用位点与调节体温的作用位点明显不同。PGE2可能参与了PH中特定位点介导的清醒神经化学机制。
