Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100193, PR China.
Insect Biochem Mol Biol. 2013 Sep;43(9):809-19. doi: 10.1016/j.ibmb.2013.06.003. Epub 2013 Jun 21.
The short neuropeptide F (sNPF), a neuropeptide in the central nervous system (CNS) of Drosophila melanogaster, is expressed in a large population of diverse neurons of brain. Most of these neurons are intrinsic interneurons of the mushroom bodies, which are the most prominent insect bilateral CNS structures that regulate memory and sleep. However, its role in sleep regulation still remains elusive. Here, we showed that sNPF-deficient female and male flies exhibit sleep enhancement with an increase of sleep bout duration. Loss of function of sNPF and sNPFR1 also elevated sleep. Moreover, the homeostatic regulation of flies after sleep deprivation was disrupted by aberrant sNPF signaling, since sleep deprivation increased transcription of sNPF and wakefulness at night in control flies but not in the sNPF mutant flies, suggesting that sNPF autoregulation plays an important role in sleep homeostasis. We further verified that sNPF signal elevated cAMP levels, and subsequently activated the downstream CREB transcription factor. The duration of sleep was found to be inversely related to cAMP signaling and CREB activity in the mushroom bodies. Thus, we concluded that sleep might be regulated by sNPF through modulating the cAMP-PKA-CREB signal pathway in vivo.
短神经肽 F（sNPF）是果蝇中枢神经系统（CNS）中的一种神经肽，在大脑中大量不同神经元中表达。这些神经元大多数是蘑菇体的固有中间神经元，蘑菇体是调节记忆和睡眠的最显著的昆虫双侧 CNS 结构。然而，它在睡眠调节中的作用仍然难以捉摸。在这里，我们表明，sNPF 缺陷的雌性和雄性苍蝇表现出睡眠增强，睡眠持续时间增加。sNPF 和 sNPFR1 的功能丧失也会增加睡眠。此外，睡眠剥夺后苍蝇的稳态调节被异常的 sNPF 信号扰乱，因为睡眠剥夺会增加控制苍蝇中 sNPF 的转录和夜间清醒，但 sNPF 突变苍蝇中不会，表明 sNPF 自身调节在睡眠稳态中起着重要作用。我们进一步验证了 sNPF 信号会升高 cAMP 水平，随后激活下游 CREB 转录因子。在蘑菇体中，发现睡眠持续时间与 cAMP 信号和 CREB 活性呈负相关。因此，我们得出结论，sNPF 可能通过调节体内的 cAMP-PKA-CREB 信号通路来调节睡眠。
