Sleep and Performance Research Center, WWAMI Medical Education Program, WA State University, Spokane, WA 99164, USA.
J Clin Sleep Med. 2011 Oct 15;7(5 Suppl):S38-42. doi: 10.5664/JCSM.1360.
Symptoms commonly associated with sleep loss and chronic inflammation include sleepiness, fatigue, poor cognition, enhanced sensitivity to pain and kindling stimuli, excess sleep and increases in circulating levels of tumor necrosis factor α (TNF) in humans and brain levels of interleukin-1 β (IL1) and TNF in animals. Cytokines including IL1 and TNF partake in non-rapid eye movement sleep (NREMS) regulation under physiological and inflammatory conditions. Administration of exogenous IL1 or TNF mimics the accumulation of these cytokines occurring during sleep loss to the extent that it induces the aforementioned symptoms. Extracellular ATP associated with neuro- and glio-transmission, acting via purine type 2 receptors, e.g., the P2X7 receptor, has a role in glia release of IL1 and TNF. These substances in turn act on neurons to change their intrinsic membrane properties and sensitivities to neurotransmitters and neuromodulators such as adenosine, glutamate and GABA. These actions change the network input-output properties, i.e., a state shift for the network. State oscillations occur locally within cortical columns and are defined using evoked response potentials. One such state, so defined, shares properties with whole animal sleep in that it is dependent on prior cellular activity--it shows homeostasis. The cortical column sleep-like state is induced by TNF and is associated with experimental performance detriments. ATP released extracellularly as a consequence of cellular activity is posited to initiate a mechanism by which the brain tracks its prior sleep-state history to induce/prohibit sleep. Thus, sleep is an emergent property of populations of local neural networks undergoing state transitions. Specific neuronal groups participating in sleep depend upon prior network use driving local network state changes via the ATP-cytokine-adenosine mechanism. Such considerations add complexity to finding biochemical markers for sleepiness.
与睡眠不足和慢性炎症相关的常见症状包括嗜睡、疲劳、认知能力下降、对疼痛和点燃刺激的敏感性增强、睡眠过多以及循环肿瘤坏死因子-α (TNF)水平升高在人类和动物的脑内白细胞介素-1β (IL1) 和 TNF。包括 IL1 和 TNF 在内的细胞因子在生理和炎症条件下参与非快速眼动睡眠 (NREMS) 的调节。外源性 IL1 或 TNF 的给药模拟了睡眠不足期间这些细胞因子的积累，以至于诱导了上述症状。与神经和神经胶质传递相关的细胞外 ATP 通过嘌呤 2 型受体（例如 P2X7 受体）作用，在神经胶质细胞释放 IL1 和 TNF 中起作用。这些物质反过来作用于神经元，改变它们对神经递质和神经调质（如腺苷、谷氨酸和 GABA）的固有膜特性和敏感性。这些作用改变了网络的输入-输出特性，即网络的状态转变。状态振荡在皮质柱内局部发生，并使用诱发反应电位来定义。这样定义的一种状态与整个动物睡眠具有相似的特性，因为它依赖于先前的细胞活动——它表现出同型性。皮质柱类似睡眠的状态由 TNF 诱导，并与实验性能下降有关。细胞活动导致细胞外释放的 ATP 被认为启动了一种机制，通过该机制大脑可以跟踪其先前的睡眠状态历史以诱导/禁止睡眠。因此，睡眠是经历状态转变的局部神经网络群体的涌现属性。参与睡眠的特定神经元群体取决于先前的网络使用，通过 ATP-细胞因子-腺苷机制驱动局部网络状态变化。这些考虑因素增加了寻找睡意生化标志物的复杂性。
