Molecular mechanisms of sleep-wake regulation and their relationships to the physiological state of the body

在大鼠和猴子身上进行了睡眠-觉醒调节的分子机制研究。重要的发现是：1。无机硒化合物对大鼠脑前列腺素D合成酶活性有抑制作用。当给药到第三脑室时，这些化合物明显抑制了大鼠的睡眠。过量的二硫苏糖醇阻断了硒对PGD合成酶活性的抑制作用以及对睡眠的抑制作用。这些结果表明，PGD_2在脑组织中合成，参与促进生理性睡眠。静脉输注这些硒化合物还能抑制大鼠的睡眠，提示这些硒化合物可用于临床治疗嗜睡症中的一些疾病。PGE_2拮抗剂AH 6809对PGE_2的唤醒作用有抑制作用，但不改变PGE_2的热作用。脑室内单独输注AH 6809可抑制清醒并增加睡眠。这些结果表明，清醒效应的PGE_2受体亚型与高温效应的PGE_2受体亚型不同，脑内生理性产生的PGE_2参与了清醒的促进和维持。在大鼠下丘脑中，有神经元随着睡眠-觉醒状态的改变而改变其活动，并对PGD_2或PGE_2的应用有特异性反应。可以想象，PGD_2和PGE_2至少在一定程度上是通过充当这些神经元的神经调节剂来调节睡眠-觉醒活动的。这些神经元在下丘脑的分布也被检查。采用近红外分光光度法对猴前脑血红蛋白氧合状态进行了连续监测。研究表明，在快速眼动睡眠期间，氧气消耗会减少。

Studies on molecular mechanisms of sleep-wake regulation were conducted in rats and monkeys. Significant findings were,1. Inorganic selenium compounds such as SeCl_4 and Na_2SeO_3 inhibited the activity of prostaglandin (PG) D synthase of the rat brain. These compounds markedly inhibited sleep of rats when administered into the third cerebral ventricle. Excess amount of dithiothreitol blocked the inhibition of PGD synthase activity as well as the inhibition of sleep by selenium. These results indicate that PGD_2 synthesized in the brain tissue is involved in the promotion of physiological sleep. Intravenous infusion of these selenium compounds also inhibited sleep of rats, suggesting that these selenium compounds can be used clinically for the therapy of some diseases categorized in hypersomnia disorders.2. AH 6809, an antagonist of PGE_2, inhibited the awaking effect of PGE_2 in rats without altering the hyperthermic effect of PGE_2. Intracerebroventricular infusion of AH 6809 alone suppressed wakefulness and increased sleep. These results suggest that the subtype of PGE_2 receptors for the awaking effect is different from the subtype for hyperthermic effect, and that PGE_2 produced physiologically in the brain is involved in the promotion and maintenance of wakefulness.3. In the hypothalamus of rats, there are neurons which change their activities along with the alterations of sleep-wake states and respond specifically to the application of PGD_2 or PGE_2. It is conceivable that PGD_2 and PGE_2 are regulating sleep-wake activities, at least in part, by acting as neuromodulators on these neurons. The distribution of these neurons in the hypothalamus was also examined.4. The oxygenation state of hemoglobin in the monkey forebrain was monitored continuously using a near-infrared spectrophotometric technique. It is suggested that oxygen consumption decreases specifically during REM sleep.