Jupiter Life Science Initiative, Florida Atlantic University, Jupiter, FL 33458, USA; Department of Biological Sciences, Florida Atlantic University, Jupiter, FL 33458, USA.
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada; Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Curr Biol. 2018 Nov 19;28(22):3700-3708.e4. doi: 10.1016/j.cub.2018.10.039. Epub 2018 Nov 8.
Sleep is critical for many aspects of brain function and is accompanied by brain-wide changes in the physiology of neurons and synapses [1, 2]. Growing evidence suggests that glial cells contribute to diverse aspects of sleep regulation, including neuronal and metabolic homeostasis [3-5], although the molecular basis for this remains poorly understood. The fruit fly, Drosophila melanogaster, displays all the behavioral and physiological characteristics of sleep [1, 2], and genetic screening in flies has identified both conserved and novel regulators of sleep and wakefulness [2, 6, 7]. With this approach, we identified Excitatory amino acid transporter 2 (Eaat2) and found that its loss from glia, but not neurons, increases sleep. We show that Eaat2 is expressed in ensheathing glia, where Eaat2 functions during adulthood to regulate sleep. Increased sleep in Eaat2-deficient flies is accompanied by reduction of metabolic rate during sleep bouts, an indicator of deeper sleep intensity. Eaat2 is a member of the conserved EAAT family of membrane transport proteins [8], raising the possibility that it affects sleep by controlling the movement of ions and neuroactive chemical messengers to and from ensheathing glia. In vitro, Eaat2 is a transporter of taurine [9], which promotes sleep when fed to flies [10]. We find that the acute effect of taurine on sleep is abolished in Eaat2 mutant flies. Together, these findings reveal a wake-promoting role for Eaat2 in ensheathing glia through a taurine-dependent mechanism.
睡眠对于大脑功能的许多方面至关重要，伴随着神经元和突触的生理变化[1,2]。越来越多的证据表明，神经胶质细胞有助于睡眠调节的各个方面，包括神经元和代谢稳态[3-5]，尽管其分子基础仍知之甚少。果蝇，Drosophila melanogaster，表现出睡眠的所有行为和生理特征[1,2]，并且在果蝇中的遗传筛选已经鉴定出睡眠和清醒的保守和新型调节剂[2,6,7]。通过这种方法，我们鉴定出兴奋性氨基酸转运体 2（Eaat2），发现其在神经胶质细胞中的缺失而不是神经元中增加了睡眠。我们表明 Eaat2 在包绕胶质细胞中表达，在成年期 Eaat2 发挥作用以调节睡眠。Eaat2 缺陷型果蝇的睡眠增加伴随着睡眠过程中代谢率的降低，这是深度睡眠强度的指标。Eaat2 是保守的 EAAT 家族膜转运蛋白的成员[8]，这表明它通过控制离子和神经活性化学信使进出包绕胶质细胞的运动来影响睡眠。在体外，Eaat2 是牛磺酸的转运体[9]，当喂食给果蝇时会促进睡眠[10]。我们发现，牛磺酸对睡眠的急性影响在 Eaat2 突变型果蝇中被消除。总之，这些发现揭示了 Eaat2 通过牛磺酸依赖的机制在包绕胶质细胞中发挥促醒作用。
