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

对睡眠-觉醒调节的分子机制进行了大鼠和猴的研究。发现：1.无机硒化合物SeCl4和Na2SeO_3对大鼠脑内前列腺素D合成酶活性有抑制作用。这些化合物在第三脑室给药时明显抑制大鼠的睡眠。过量的二硫苏糖醇阻断了对PGD合成酶活性的抑制和硒对睡眠的抑制。这些结果表明，脑组织合成的PGD2参与了生理睡眠的促进。结论：1.静脉滴注这些硒化合物对大鼠的睡眠也有抑制作用，提示这些硒化合物可用于临床治疗某些睡眠过多的疾病。PGE_2的拮抗剂AH 6809可抑制PGE_2对大鼠的唤醒作用，但不改变PGE_2的升温作用。单侧脑室注射AH 6809可抑制觉醒和增加睡眠。这些结果提示，觉醒效应的PGE_2受体亚型不同于热效应的PGE_2受体亚型，脑内生理性产生的PGE_2参与觉醒的促进和维持。在大鼠下丘脑中，有一些神经元随着睡眠-觉醒状态的改变而改变其活动，并对PGD_2或PGE_2的应用作出特异性的反应。可以想象，PGD_2和PGE_2至少部分地通过对这些神经元起神经调节剂的作用来调节睡眠-觉醒活动。并观察了这些神经元在下丘脑的分布。用近红外分光光度技术连续监测猴前脑内血红蛋白的氧合状态。提示在快速眼动睡眠过程中，氧耗量下降尤为明显。

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.