Yamaguchi Sho T, Tomita Jun, Kume Kazuhiko
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.
Biochem Biophys Res Commun. 2022 Feb 5;591:44-49. doi: 10.1016/j.bbrc.2021.12.100. Epub 2021 Dec 28.
Sleep relates to numerous biological functions, including metabolism. Both dietary conditions and genes related to metabolism are known to affect sleep behavior. Insulin signaling is well conserved across species including the fruit fly and relates to both metabolism and sleep. However, the neural mechanism of sleep regulation by insulin signaling is poorly understood. Here, we report that insulin signaling in specific neurons regulates sleep in Drosophila melanogaster. We analyzed the sleep behavior of flies with the mutation in insulin-like ligands expressed in the brain and found that three insulin-like ligands participate in sleep regulation with some redundancy. We next used 21 Gal4 drivers to express a dominant-negative form of the insulin receptor (InR DN) in various neurons including circadian clock neurons, which express the clock gene, and the pars intercerebralis (PI). Inhibition of insulin signaling in the anterior dorsal neuron group 1 (DN1a) decreased sleep. Additionally, the same manipulation in PI also decreased sleep. Pan-neuronal induced expression of InR DN also decreased sleep. These results suggested that insulin signaling in DN1a and PI regulates sleep.
睡眠与包括新陈代谢在内的众多生物学功能相关。已知饮食条件和与新陈代谢相关的基因都会影响睡眠行为。胰岛素信号在包括果蝇在内的物种中高度保守，且与新陈代谢和睡眠都有关系。然而，胰岛素信号调节睡眠的神经机制却知之甚少。在此，我们报告特定神经元中的胰岛素信号调节黑腹果蝇的睡眠。我们分析了大脑中表达的胰岛素样配体发生突变的果蝇的睡眠行为，发现三种胰岛素样配体以某种冗余方式参与睡眠调节。接下来，我们使用21种Gal4驱动子在包括表达生物钟基因的生物钟神经元和脑间部（PI）在内的各种神经元中表达胰岛素受体（InR DN）的显性负性形式。抑制前背神经元组1（DN1a）中的胰岛素信号会减少睡眠。此外，在PI中进行相同操作也会减少睡眠。全神经元诱导表达InR DN也会减少睡眠。这些结果表明，DN1a和PI中的胰岛素信号调节睡眠。
