AANAT1 functions in astrocytes to regulate sleep homeostasis.
AANAT1 functions in astrocytes to regulate sleep homeostasis.
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DOI：
10.7554/elife.53994
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发表时间：
2020-09-21
期刊：
影响因子：
7.7
通讯作者：
van Meyel DJ
中科院分区：
文献类型：
--
作者：
Davla S;Artiushin G;Li Y;Chitsaz D;Li S;Sehgal A;van Meyel DJ
大脑如何控制长时间清醒后恢复睡眠的需要和获得是睡眠研究中的一个重要问题。单胺类物质5-羟色胺和多巴胺是哺乳动物和果蝇睡眠的关键调节剂。我们发现，酶芳基烷基胺N-乙酰转移酶1（AANAT 1）表达的果蝇星形胶质细胞和特定子集的神经元在成年人的大脑。AANAT 1乙酰化单胺并使其失活，我们发现AANAT 1限制了睡眠剥夺（SD）时大脑中5-羟色胺和多巴胺的积累。AANAT 1从星形胶质细胞而不是从神经元的损失，导致苍蝇增加他们的白天恢复睡眠后过夜SD。总之，这些发现证明了AANAT 1和星形胶质细胞在调节单胺生物利用度和稳态睡眠中的关键作用。睡眠对我们的身心健康至关重要。睡眠不足会影响我们的精力和注意力水平，通常与慢性疾病和情绪障碍有关。睡眠是由我们大脑中的内部时钟控制的，它以24小时为周期运行，告诉我们的身体什么时候累了，准备睡觉，或者新鲜而警觉地开始新的一天。此外，大脑跟踪睡眠需求，并在长时间清醒后推动睡眠的恢复-这一过程被称为睡眠-清醒稳态。大脑中的化学信使，如多巴胺和血清素，在调节我们的睡眠动力方面也起着重要作用。虽然多巴胺让我们保持清醒，但血清素既可以防止我们入睡，也可以帮助我们入睡，这取决于它被释放的大脑部分。大多数研究都集中在不同的大脑回路对睡眠的作用上，但有研究表明，某种类型的脑细胞，称为星形胶质细胞，可能对睡眠调节也很重要。到目前为止，还不清楚星形胶质细胞是否参与调节睡眠不足后恢复睡眠的需要-也称为反弹睡眠。现在，Davla，Artiushin等人使用睡眠剥夺的果蝇来进一步研究这一点。果蝇保持清醒超过12小时（从下午6点到早上6点），使用间歇性物理搅动。研究人员发现，果蝇大脑中的星形胶质细胞表达一种名为AANAT 1的分子，该分子在夜晚开始时达到峰值，随着夜晚的推移而下降，并在早晨恢复。在睡眠不足的果蝇中，它使化学信使失活，从而降低了大脑中多巴胺和血清素的含量。然而，在缺乏AANAT 1的突变果蝇中，睡眠剥夺后大脑中的多巴胺和5-羟色胺水平都增加了。当选择性地从星形胶质细胞中去除AANAT 1时，睡眠剥夺的果蝇在白天需要更多的反弹睡眠来弥补晚上失去的睡眠。这表明星形胶质细胞和AANAT 1在睡眠稳态中起着关键作用。属于AANAT家族的分子存在于苍蝇和人类中，这些结果可能对睡眠科学产生重要影响。Davla，Artiushin等人的研究为理解两种生物体中相似的睡眠稳态机制铺平了道路，并且可能在未来有助于识别针对星形胶质细胞及其表达的分子的睡眠药物。
How the brain controls the need and acquisition of recovery sleep after prolonged wakefulness is an important issue in sleep research. The monoamines serotonin and dopamine are key regulators of sleep in mammals and in Drosophila. We found that the enzyme arylalkylamine N-acetyltransferase 1 (AANAT1) is expressed by Drosophila astrocytes and specific subsets of neurons in the adult brain. AANAT1 acetylates monoamines and inactivates them, and we found that AANAT1 limited the accumulation of serotonin and dopamine in the brain upon sleep deprivation (SD). Loss of AANAT1 from astrocytes, but not from neurons, caused flies to increase their daytime recovery sleep following overnight SD. Together, these findings demonstrate a crucial role for AANAT1 and astrocytes in the regulation of monoamine bioavailability and homeostatic sleep. Sleep is essential for our physical and mental health. A lack of sleep can affect our energy and concentration levels and is often linked to chronic illnesses and mood disorders. Sleep is controlled by an internal clock in our brain that operates on a 24-hour cycle, telling our bodies when we are tired and ready for bed, or fresh and alert to start a new day. In addition, the brain tracks the need for sleep and drives the recovery of sleep after periods of prolonged wakefulness – a process known as sleep-wake homeostasis. Chemical messengers in the brain such as dopamine and serotonin also play an important part in regulating our sleep drive. While dopamine keeps us awake, serotonin can both prevent us from and help us falling asleep, depending on the part of the brain in which it is released. Most research has focused on the role of different brain circuits on sleep, but it has been shown that a certain type of brain cell, known as astrocyte, may also be important for sleep regulation. So far, it has been unclear if astrocytes could be involved in regulating the need for recovery sleep after a sleep-deprived night – also known as rebound sleep. Now, Davla, Artiushin et al. used sleep-deprived fruit flies to investigate this further. The flies were kept awake over 12 hours (from 6pm to 6am), using intermittent physical agitation. The researchers found that astrocytes in the brains of fruit flies express a molecule called AANAT1, which peaked at the beginning of the night, declined as the night went on and recovered by morning. In sleep deprived flies, it inactivated the chemical messengers and so lowered the amount of dopamine and serotonin in the brain. However, in mutant flies that lacked AANAT1, both dopamine and serotonin levels increased in the brain after sleep deprivation. When AANAT1 was selectively removed from astrocytes only, sleep-deprived flies needed more rebound sleep during the day to make up for lost sleep at night. This shows that both astrocytes and AANAT1 play a crucial role in sleep homeostasis. Molecules belonging to the AANAT family exist in both flies and humans, and these results could have important implications for the science of sleep. The study of Davla, Artiushin et al. paves the way for understanding the mechanisms of sleep homeostasis that are similar in both organisms, and may in the future, help to identify sleep drugs that target astrocytes and the molecules they express.