中国科学院脑科学与智能技术卓越创新中心刘丹倩小组的一项最新研究揭示了中脑睡眠神经元中的过氧化氢调节睡眠稳态。相关论文发表在2025年5月15日出版的《细胞—代谢》杂志上。

该研究团队发现，小鼠急性睡眠剥夺（SD）会导致大脑氧化的普遍增加，尤其是在促进睡眠的区域。细胞内过氧化氢（H₂O₂）实时动态的体内成像显示，在黑质睡眠神经元中，胞质过氧化氢（H₂O₂）的增加反映了睡眠债务，而不是线粒体过氧化氢的增加，并通过与清醒时间呈正相关来跟踪自发觉醒。通过控制神经元内的H₂O₂，该团队发现H₂O₂的升高是代偿性睡眠所必需的，并且至少部分依赖于瞬时受体电位美拉抑素2（TRPM2）通道。

然而，过量的H₂O₂会引起脑炎症和睡眠碎片化。总之，他们的研究证明了神经元内H₂O₂是将大脑氧化还原失衡转化为睡眠驱动的关键信号分子，并强调了氧化应激在睡眠稳态中的重要性。

据介绍，睡眠可以保护动物免受氧化损伤，但氧化还原状态和睡眠稳态之间的动态相互作用尚不清楚。

附：英文原文

Title: Hydrogen peroxide in midbrain sleep neurons regulates sleep homeostasis

Author: Yujing Tian, Luwei Kang, Ngoc T. Ha, Juan Deng, Danqian Liu

Issue&Volume: 2025-05-15

Abstract: Sleep could protect animals from oxidative damage, yet the dynamic interplay between the redox state and sleep homeostasis remains unclear. Here, we show that acute sleep deprivation (SD) in mice caused a general increase in brain oxidation, particularly in sleep-promoting regions. In vivo imaging of intracellular hydrogen peroxide (H2O2) real-time dynamics revealed that in nigra sleep neurons, the increase in cytosolic but not mitochondrial H2O2 reflects sleep debt and tracks spontaneous wakefulness by positively correlating with wake duration. By controllably manipulating intraneuronal H2O2, we discovered that H2O2 elevation is required for compensatory sleep and causally promotes sleep initiation, at least partly dependent on transient receptor potential melastatin 2 (TRPM2) channel. However, excessive H2O2 induced brain inflammation and sleep fragmentation. Together, our study demonstrates intraneuronal H2O2 as a crucial signaling molecule that translates brain redox imbalance into sleep drive and underscores the significance of oxidative eustress in sleep homeostasis.

DOI: 10.1016/j.cmet.2025.04.016

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00254-2