Role of d-serine in intestinal ROS accumulation after sleep deprivation

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-18 DOI:10.1126/sciadv.adr8592

Feng Zheng, Shuai Liu, Tian Wei, Lei Wang, Yuanyuan Chang, Hao Qu, Lei Zheng

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Abstract

Prolonged sleep deprivation (SD) results in increased accumulation of reactive oxygen species (ROS) in gut, although the underlying mechanisms remain to be elucidated. This study identifies d-serine as a crucial regulator of gut ROS during SD. Knockdown of serine racemase (SR), the enzyme responsible for d-serine production, prevents the enhanced ROS buildup during SD in Drosophila. Gut enterocytes (ECs) respond to γ-aminobutyric acid (GABA) signaling by producing d-serine, which influences downstream N-methyl-d-aspartate receptor (NMDAR) activity and modulates sleep pressure. However, the continuous demand for sleep disrupts this feedback loop. Prolonged SD leads to increased levels of d-serine in the gut, an elevated pyruvate pool in ECs, enhanced mitochondrial oxidative phosphorylation, impaired lipid metabolism in peroxisomes, and the accumulation of harmful ROS. In conclusion, our findings illuminate the metabolic alterations and brain-gut communication pathways that may contribute to the increase in gut d-serine and subsequent ROS accumulation induced by SD.

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d-丝氨酸在睡眠剥夺后肠道ROS积累中的作用

长时间睡眠剥夺（SD）导致肠道活性氧（ROS）积累增加，尽管其潜在机制仍有待阐明。本研究确定d-丝氨酸是SD期间肠道ROS的重要调节因子。丝氨酸消旋酶（SR）是一种负责d-丝氨酸产生的酶，它的敲低可以防止果蝇SD期间ROS的增强积累。肠道细胞通过产生d-丝氨酸响应γ-氨基丁酸（GABA）信号，影响下游n -甲基-d-天冬氨酸受体（NMDAR）活性并调节睡眠压力。然而，持续的睡眠需求破坏了这种反馈循环。延长SD导致肠道d-丝氨酸水平升高，ECs中丙酮酸池升高，线粒体氧化磷酸化增强，过氧化物酶体脂质代谢受损，有害ROS积累。总之，我们的研究结果阐明了代谢改变和脑-肠通讯途径可能有助于SD诱导的肠道d-丝氨酸增加和随后的ROS积累。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.