University of Lyon, Faculty of Medicine, Neurosciences Research Center of Lyon, 8 Avenue Rockefeller, F-69373 Lyon, France.
Sleep Med Rev. 2012 Jun;16(3):265-79. doi: 10.1016/j.smrv.2012.01.006. Epub 2012 Mar 8.
Nitric oxide (NO) production involves four different NO-synthases (NOSs) that are either constitutive (neuronal, nNOS; endothelial, eNOS; mitochondrial, mNOS) or inducible (iNOS) in nature. Three main processes regulate NO/NOSs output, i.e., the L-arginine/arginase substrate-competing system, the L-citrulline/arginosuccinate-recycling system and the asymmetric dimethyl-/monomethyl-L-arginine-inhibiting system. In adult animals, nNOS exhibits a dense innervation intermingled with pontine sleep structures. It is well established that the NO/nNOS production makes a key contribution to daily homeostatic sleep (slow-wave sleep, SWS; rapid eye movement sleep, REM sleep). In the basal hypothalamus, the NO/nNOS production further contributes to the REM sleep rebound that takes place after a sleep deprivation (SD). This production may also contribute to the sleep rebound that is associated with an immobilization stress (IS). In adult animals, throughout the SD time-course, an additional NO/iNOS production takes place in neurons. Such production mediates a transitory SD-related SWS rebound. A transitory NO/iNOS production is also part of the immune system. Such a production contributes to the SWS increase that accompanies inflammatory events and is ensured by microglial cells and astrocytes. Finally, with aging, the iNOS expression becomes permanent and the corresponding NO/iNOS production is important to ensure an adequate maintenance of REM sleep and, to a lesser extent, SWS. Despite such maintenance, aged animals, however, are not able to elicit a sleep rebound to deal with the challenge of SD or IS. Sleep regulatory processes in adult animals thus become impaired with age. Reduced iNOS expression during aging may contribute to accelerated senescence, as observed in senescence-accelerated mice (SAMP-8 mice).
一氧化氮（NO）的产生涉及四种不同的一氧化氮合酶（NOS），它们要么是组成型的（神经元型、nNOS；内皮型、eNOS；线粒体型、mNOS），要么是诱导型的（iNOS）。有三个主要过程调节 NO/NOS 的产生，即 L-精氨酸/精氨酸酶底物竞争系统、L-瓜氨酸/精氨琥珀酸再循环系统和不对称二甲基-/单甲基-L-精氨酸抑制系统。在成年动物中，nNOS 表现出与脑桥睡眠结构交织在一起的密集神经支配。众所周知，NO/nNOS 的产生对日常的稳态睡眠（慢波睡眠，SWS；快速眼动睡眠，REM 睡眠）做出了关键贡献。在基础下丘脑，NO/nNOS 的产生进一步促进了睡眠剥夺（SD）后的 REM 睡眠反弹。这种产生也可能与固定应激（IS）相关的睡眠反弹有关。在成年动物中，在整个 SD 过程中，神经元中会产生额外的 NO/iNOS。这种产生介导了与 SD 相关的短暂 SWS 反弹。NO/iNOS 的短暂产生也是免疫系统的一部分。这种产生有助于伴随着炎症事件的 SWS 增加，并由小胶质细胞和星形胶质细胞来保证。最后，随着年龄的增长，iNOS 的表达变得持久，相应的 NO/iNOS 的产生对于确保 REM 睡眠的充分维持以及在较小程度上确保 SWS 的维持是重要的。尽管有这种维持，但老年动物仍然无法引起睡眠反弹来应对 SD 或 IS 的挑战。因此，成年动物的睡眠调节过程会随着年龄的增长而受损。衰老过程中 iNOS 表达的减少可能会导致衰老加速，正如在衰老加速小鼠（SAMP-8 小鼠）中观察到的那样。
