AKH-FOXO pathway regulates starvation-induced sleep loss through remodeling of the small ventral lateral neuron dorsal projections.
AKH-FOXO pathway regulates starvation-induced sleep loss through remodeling of the small ventral lateral neuron dorsal projections.
复制标题
DOI：
10.1371/journal.pgen.1009181
复制
发表时间：
2020-10
期刊：
影响因子：
4.5
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
He Q;Du J;Wei L;Zhao Z
据报道，由不利的喂养压力或食物短缺引起的饥饿会导致动物睡眠不足。然而，饥饿信号如何与中枢神经系统相互作用仍不清楚。在这里，脂肪运动激素(AKH)-Fork Head Box-O(FOXO)通路被证明通过重塑S-LNV(小腹侧神经元)背部投射来响应能量变化并调节果蝇的睡眠。我们的结果表明，饥饿会阻止苍蝇在第一次明暗转换后入睡。LNV是饥饿引起的睡眠丧失所必需的，通过延伸含有色素分散因子的S-LNV背侧投射。进一步的研究表明，AKH或AKHR(AKH受体)功能的丧失阻断了饥饿诱导的S-LNV背侧投射的延长，并挽救了食物缺乏时的睡眠抑制。FOXO是AKH下游的饥饿反应因子，具有调节神经元突触可塑性的作用，下调FOXO水平可显著减轻饥饿对S-LNV背侧投射和睡眠的影响。综上所述，我们的结果概述了饥饿信号和睡眠之间的转导途径，并揭示了一个新的睡眠调节功能位点。果蝇的睡眠受昼夜节律和动态平衡的调节在正常情况下，在细胞应激或损伤的情况下，中枢神经系统神经元根据冲动调节睡眠，冲动是由周围组织或神经系统细胞产生的细胞因子产生的神经肽传递的。新陈代谢与睡眠有着千丝万缕的联系，能量缺乏对睡眠有巨大的影响，饥饿引起的果蝇睡眠丧失已有报道，许多基因在这一过程中发挥作用。然而，饥饿信号是如何传递到神经系统，进而导致失眠的，目前还不清楚。在本研究中，我们发现饥饿阻止了果蝇进入睡眠，饥饿引起的睡眠丧失需要PDFFR和LNVS，饥饿时果蝇比正常条件下表现出更多的S-LNVS背侧投射。LNV是重要的觉醒神经元，它们通过背侧投射将唤醒信号传递到下游神经元，更广泛的S-LNVS背侧投射加速觉醒信号的传递，可以阻止苍蝇进入睡眠状态。丧失AKH/AKHR/FOXO功能的苍蝇可以限制饥饿引起的睡眠损失。阻断AKH-FOXO通路的果蝇也能限制饥饿诱导的S-LNVS背投射开放，提示S-LNVS背投射是饥饿信号调节睡眠的功能部位。
Starvation caused by adverse feeding stresses or food shortages has been reported to result in sleep loss in animals. However, how the starvation signal interacts with the central nervous system is still unknown. Here, the adipokinetic hormone (AKH)—Fork head Box-O (FOXO) pathway is shown to respond to energy change and adjust the sleep of Drosophila through remodeling of the s-LNv (small ventral lateral neurons) dorsal projections. Our results show that starvation prevents flies from going to sleep after the first light-dark transition. The LNvs are required for starvation-induced sleep loss through extension of the pigment dispersing factor (PDF)-containing s-LNv dorsal projections. Further studies reveal that loss of AKH or AKHR (akh receptor) function blocks starvation-induced extension of s-LNv dorsal projections and rescues sleep suppression during food deprivation. FOXO, which has been reported to regulate synapse plasticity of neurons, acts as starvation response factor downstream of AKH, and down regulation of FOXO level considerably alleviates the influence of starvation on s-LNv dorsal projections and sleep. Taking together, our results outline the transduction pathways between starvation signal and sleep, and reveal a novel functional site for sleep regulation. Sleep of Drosophila is regulated by circadian rhythm and homeostasis on the normal condition, in the presence of cellular stress or injury, the central nervous system neurons adjust sleep on the basis of impulse, which is transmitted by neuropeptides generated by cytokines from either peripheral tissues or nervous system cells. Metabolism and sleep are inextricably linked, energy deficiency has an enormous impact on the sleep, starvation induced sleep loss in the Drosophila has been reported and many genes play roles in this process. However, how the starvation signals transmit to nervous system and then make the sleep loss are still no clear. In this study we find the starvation prevent flies going to sleep, PDF/PDFR and LNvs are required for starvation induced sleep loss, during starvation flies show more expanded s-LNvs dorsal projection compared to flies on the normal condition. LNvs are vital awakening neurons, they transmit arousal signal to downstream neurons through its dorsal projections, more patulous s-LNvs dorsal projections accelerate the transmission of awakening signals, can prevent flies from going to sleep. Flies losing AKH/AKHR/FOXO function limit starvation induced sleep loss. Flies with blocked AKH-FOXO pathway also limit starvation induced s-LNvs dorsal projections opening, indicating that the s-LNvs dorsal projections are function sites of starvation signal on sleep regulation.
登录
查看更多内容
影响因子：
16.6
作者：
Chen X;Rosbash M
通讯作者：
Rosbash M
影响因子：
9.8
作者：
Grönke S;Müller G;Hirsch J;Fellert S;Andreou A;Haase T;Jäckle H;Kühnlein RP
通讯作者：
Kühnlein RP
影响因子：
8.8
作者：
Chung BY;Ro J;Hutter SA;Miller KM;Guduguntla LS;Kondo S;Pletcher SD
通讯作者：
Pletcher SD
影响因子：
3.3
作者：
Bringmann H
通讯作者：
Bringmann H
DOI：
10.1016/j.cub.2010.05.029
发表时间：
2010-07-13
期刊：
Current biology : CB
影响因子：
--
作者：
Keene AC;Duboué ER;McDonald DM;Dus M;Suh GS;Waddell S;Blau J
通讯作者：
Blau J