一个综合的模型,为支持稳态睡眠信号的聚合生物学提供支持

IF 3.4 2区 医学 Q1 CLINICAL NEUROLOGY
Fabian-Xosé Fernandez , Michael A. Grandner
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引用次数: 0

摘要

长期以来,睡眠一直被认为是一个主要由中枢机制调节的过程,包括体内平衡压力和昼夜节律。然而,新兴的研究表明,骨骼肌积极参与睡眠调节,作为一种内分泌器官,释放能够影响大脑功能的生物活性分子。本文综述了越来越多的证据支持肌肉来源对睡眠稳态的贡献,重点关注关键信号分子,如白介素-6 (IL-6)、血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)、鸢尾素、乳酸和甲基乙二醛。我们探索了它们的分子途径、受体相互作用以及与成熟的睡眠中枢调节因子(包括腺苷和细胞因子信号网络)的整合。令人信服的遗传证据,特别是来自操纵肌肉中Bmal1表达的研究,表明外周组织可以独立于大脑的中心机制调节睡眠深度和恢复。这些发现支持了骨骼肌作为疲劳系统传感器的观点,将代谢和炎症信号传递给大脑,帮助校准睡眠需求。认识到这种肌肉-大脑的相互作用为转化研究开辟了新的方向,包括以运动为基础的疗法和针对肌因子途径的药物策略,以提高睡眠质量。这一不断发展的观点挑战了传统的观点,即睡眠是一个完全由大脑控制的过程,将骨骼肌定位为睡眠-觉醒动力学的活跃和必要的调节器。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A comprehensive model for the converging biologies that underpin the homeostatic sleep signal
Sleep has long been understood as a process regulated primarily by central mechanisms, including homeostatic pressure and circadian rhythms. However, emerging research reveals that skeletal muscle actively participates in sleep regulation, functioning as an endocrine organ that releases bioactive molecules capable of influencing brain function. This review examines the growing body of evidence supporting a muscle-derived contribution to sleep homeostasis, focusing on key signaling molecules such as interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), irisin, lactate, and methylglyoxal. We explore their molecular pathways, receptor interactions, and integration with well-established central regulators of sleep, including adenosine and cytokine signaling networks. Compelling genetic evidence, particularly from studies manipulating Bmal1 expression specifically in muscle, demonstrates that peripheral tissues can modulate sleep depth and recovery independently of the brain's central mechanisms. These findings support the idea that skeletal muscle functions as a systemic sensor of fatigue, relaying metabolic and inflammatory cues to the brain that help calibrate sleep need. Recognizing this muscle–brain crosstalk opens new directions for translational research, including exercise-based therapies and pharmacological strategies targeting myokine pathways to enhance sleep quality. This evolving perspective challenges the traditional view of sleep as a process governed solely by the brain, positioning skeletal muscle as an active and essential regulator of sleep–wake dynamics.
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来源期刊
Sleep medicine
Sleep medicine 医学-临床神经学
CiteScore
8.40
自引率
6.20%
发文量
1060
审稿时长
49 days
期刊介绍: Sleep Medicine aims to be a journal no one involved in clinical sleep medicine can do without. A journal primarily focussing on the human aspects of sleep, integrating the various disciplines that are involved in sleep medicine: neurology, clinical neurophysiology, internal medicine (particularly pulmonology and cardiology), psychology, psychiatry, sleep technology, pediatrics, neurosurgery, otorhinolaryngology, and dentistry. The journal publishes the following types of articles: Reviews (also intended as a way to bridge the gap between basic sleep research and clinical relevance); Original Research Articles; Full-length articles; Brief communications; Controversies; Case reports; Letters to the Editor; Journal search and commentaries; Book reviews; Meeting announcements; Listing of relevant organisations plus web sites.
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