Neurofibromin 1 mediates sleep depth in Drosophila.
Neurofibromin 1 mediates sleep depth in Drosophila.
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DOI：
10.1371/journal.pgen.1011049
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发表时间：
2023-12
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
睡眠和代谢稳态的神经调节在人类健康的许多方面都是至关重要的。尽管有广泛的流行病学证据表明睡眠失调与肥胖、糖尿病和代谢综合征有关，但人们对睡眠和代谢功能整合的神经和分子基础知之甚少。RAS gtpase激活基因神经纤维蛋白（Nf1）与睡眠和代谢率的调节有关，提高了它整合这些过程的可能性，但对睡眠巩固和生理的影响仍然知之甚少。哺乳动物和苍蝇睡眠深度的一个关键标志是睡眠时代谢率的降低。在这里，我们检查了睡眠质量的多种测量方法，以确定Nf1对唤醒阈值和代谢率的睡眠依赖性变化的影响。缺乏Nf1的果蝇在睡眠中无法抑制代谢率，因此Nf1的缺失可能会阻碍果蝇整合睡眠和代谢状态。Nf1突变果蝇的睡眠是碎片化的，Nf1突变果蝇的唤醒阈值降低，这表明Nf1突变果蝇无法进入深度睡眠。Nf1对睡眠的影响可能局限于表达GABAA受体Rdl的神经元子集。在果蝇和哺乳动物中，睡眠不足与肠道内平衡的变化有关。神经系统中表达rdl的神经元中Nf1的选择性下调会增加肠道通透性和肠道中的活性氧（ROS），从而增加了睡眠质量下降导致肠道失调的可能性。总之，这些发现表明Nf1在gaba敏感神经元中起作用，调节果蝇的睡眠深度。越来越多的证据表明，果蝇和哺乳动物一样，拥有不同形式的睡眠，包括浅睡眠和深度睡眠。尽管我们对调节睡眠时间的基因的理解取得了重大进展，但我们对不同形式的睡眠是如何被调节的知之甚少。神经纤维蛋白1与许多神经表型相关，包括睡眠失调和昼夜节律失调。在这里，我们报告了携带神经纤维蛋白1突变的果蝇无法进入深度睡眠。这种表型可以定位于大脑中的gaba受体神经元，这些神经元中神经纤维蛋白1的选择性丧失也与寿命缩短和肠道失调有关。总之，这些发现为果蝇睡眠深度的神经基础提供了见解。
Neural regulation of sleep and metabolic homeostasis are critical in many aspects of human health. Despite extensive epidemiological evidence linking sleep dysregulation with obesity, diabetes, and metabolic syndrome, little is known about the neural and molecular basis for the integration of sleep and metabolic function. The RAS GTPase-activating gene Neurofibromin (Nf1) has been implicated in the regulation of sleep and metabolic rate, raising the possibility that it serves to integrate these processes, but the effects on sleep consolidation and physiology remain poorly understood. A key hallmark of sleep depth in mammals and flies is a reduction in metabolic rate during sleep. Here, we examine multiple measures of sleep quality to determine the effects of Nf1 on sleep-dependent changes in arousal threshold and metabolic rate. Flies lacking Nf1 fail to suppress metabolic rate during sleep, raising the possibility that loss of Nf1 prevents flies from integrating sleep and metabolic state. Sleep of Nf1 mutant flies is fragmented with a reduced arousal threshold in Nf1 mutants, suggesting Nf1 flies fail to enter deep sleep. The effects of Nf1 on sleep can be localized to a subset of neurons expressing the GABAA receptor Rdl. Sleep loss has been associated with changes in gut homeostasis in flies and mammals. Selective knockdown of Nf1 in Rdl-expressing neurons within the nervous system increases gut permeability and reactive oxygen species (ROS) in the gut, raising the possibility that loss of sleep quality contributes to gut dysregulation. Together, these findings suggest Nf1 acts in GABA-sensitive neurons to modulate sleep depth in Drosophila. Growing evidence suggests fruit flies, like mammals, possess different forms of sleep including light and deep sleep. Despite major advances in our understanding of t genes regulating sleep duration, little is known about how different forms of sleep are regulated. Neurofibramin 1 is associated with numerous neurological phenotypes including dysregulated sleep and circadian rhythms. Here, we report that flies harboring mutations in Neurofibramin 1 fail to enter deep sleep. This phenotype can be localized to GABA-receptive neurons in the brain and selective loss of Neurofibramin 1 in these neurons is also associated with reduced longevity and gut dysregulation. Together, these findings provide insight into the neural basis of sleep depth in fruit flies.
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影响因子：
4.6
作者：
Tritz R;Hudson FZ;Harris V;Ghoshal P;Singla B;Lin H;Csanyi G;Stansfield BK
通讯作者：
Stansfield BK
影响因子：
2.4
作者：
Bushey D;Hughes KA;Tononi G;Cirelli C
通讯作者：
Cirelli C
睡眠通过阻止多巴胺神经元介导的遗忘来促进记忆。
影响因子：
64.5
作者：
Berry JA;Cervantes-Sandoval I;Chakraborty M;Davis RL
通讯作者：
Davis RL
影响因子：
16.6
作者：
Botero V;Stanhope BA;Brown EB;Grenci EC;Boto T;Park SJ;King LB;Murphy KR;Colodner KJ;Walker JA;Keene AC;Ja WW;Tomchik SM
通讯作者：
Tomchik SM
影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L