Functional Changes Induced By Sleep Deprivation

睡眠的功能在当今的生物学中是一个真正的谜。 这些功能可以通过防止睡眠发生来研究。 在大鼠中，长时间的完全或快速眼动睡眠剥夺导致极度嗜睡、体重减轻、食物摄入量和代谢率增加，并在2-5周后死亡。 几十年的研究都没有发现任何实质性的异常，在外周器官或大脑。在过去的几年里，分子方法已经被用来研究睡眠和清醒的细胞相关性。几种化合物已被证明在清醒期间和短时间的睡眠衍生后积累，并在睡眠期间恢复到基础水平，与睡眠调节的稳态模型一致。 为了评估这些发现在睡眠稳态背景下的功能意义，新的基因筛选方法，如微阵列和差异显示已被用于检查短期和长期睡眠剥夺后的基因表达。 虽然大多数基因筛选（约10000）没有修改，大脑芳基磺基转移酶（AST）的水平增加了短时间的清醒，甚至更长的睡眠衍生。 这种酶负责去甲肾上腺素的失活，去甲肾上腺素在清醒时在大脑中释放，在NREM和REM睡眠期间释放得更少。 因此，AST的诱导可能构成脑对中枢去甲肾上腺素能系统的不间断活动的稳态反应的第一个指示。 将通过检查AST mRNA是否（1）随着完全睡眠剥夺的时间而逐渐增加，在选择性REM睡眠衍生后增加，并在恢复睡眠后恢复正常;（2）伴随中枢去甲肾上腺素周转增加的指数;（3）在中枢去甲肾上腺素能系统损伤的动物中减少来检验这一假设。 最后，将确定受损动物是否对睡眠剥夺的有害影响更具抵抗力。这些研究应该为长期睡眠剥夺和慢性失眠的分子后果提供见解，并提出新的治疗方法。

The functions of sleep constitute a genuine mystery in present day biology. Such functions can be investigated by preventing sleep from occurring. In rats, prolonged total or REM sleep deprivation lead to extreme sleepiness, weight loss, increase in food intake and metabolic rate, and death after 2-5 weeks. Decades of investigation have failed to reveal any substantial abnormality in peripheral organs or in the brain. Over the past few years, molecular approaches have been employed the to study the cellular correlates of sleep and waking. Several compounds have been shown to accumulate during waking and after short periods of sleep derivation and to return to basal levels during sleep, in line with homoeostatic models of sleep regulation. To evaluate the functional significance of these findings in the context of sleep homeostasis, new gene screening methods such as microarrays and differential display have been used to examine gene expression after both short-and long-term sleep deprivation. While most genes screened (approximately 10000) were not modified, the levels of brain arylsulfotransferase (AST) were increased by short periods of waking and even more so by prolonged sleep derivation. This enzyme is responsible for the inactivation of noradrenaline, which is released in the brain during waking and much less during NREM and REM sleep. The induction of AST may thus constitute a first indication of a homoeostatic response by the brain to the uninterrupted activity of the central noradrenergic system. This hypothesis will be tested by examining whether AST mRNA (1) progressively increases with the length of total sleep deprivation, increases after selective REM sleep derivation, and returns to normal after recovery sleep; (2) is accompanied by indices of increased central noradrenaline turnover; and (3) is reduced in animals with lesions of the central noradrenergic system. Finally, it will be established whether lesioned animals are more resistant to the harmful effects of sleep deprivation. These studies should provide insights into the molecular consequences of prolonged sleep deprivation and chronic insomnia and suggest new therapeutic approaches.