Properties of REM sleep alterations with epilepsy
Properties of REM sleep alterations with epilepsy
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DOI：
10.1093/brain/awac499
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发表时间：
2023-02-24
期刊：
影响因子：
14.5
通讯作者：
Matsui, Ko
中科院分区：
文献类型：
--
作者：
Ikoma, Yoko;Takahashi, Yusuke;Matsui, Ko
人们通常认为人在睡眠中休息。然而，在REM睡眠期间，可能需要高能量消耗的协调神经活动增加。在这里，使用自由移动的雄性转基因小鼠，在REM睡眠期间的局部大脑环境和星形胶质细胞活动使用纤维光度法进行检查，该方法将光纤插入外侧下丘脑深处，该区域与控制整个大脑的睡眠和代谢状态有关。检查脑实质内源性自发荧光或星形胶质细胞中表达的Ca 2+或pH传感器的荧光的光学波动。使用一种新设计的分析方法，在星形胶质细胞胞浆Ca 2+和pH值的变化和局部脑血容量（BBV）的变化进行了提取。在REM睡眠中，星形胶质细胞Ca 2+减少，pH降低（酸化）和BBV增加。酸化是出乎意料的，因为BBV的增加将导致有效的二氧化碳和/或乳酸盐去除，这导致局部脑环境的碱化。酸化可能是由于星形胶质细胞中神经元活性增强和/或有氧代谢导致谷氨酸转运蛋白活性增加的结果。值得注意的是，光学信号变化先于REM睡眠的电生理特性特征的开始，大约20-30秒。这表明局部大脑环境的变化对神经元细胞活动的状态有很强的控制作用。随着海马的反复刺激，癫痫发作反应通过点燃逐渐发展。在用多天的刺激获得完全点燃状态后，再次检查外侧下丘脑的REM睡眠的光学特性。尽管在点燃后的REM睡眠期间观察到检测到的光信号的负偏转，但估计的分量改变。Ca 2+的减少和BBV的增加是最小的，pH值（酸化）出现大幅下降。这种酸性转变可能会触发星形胶质细胞释放额外的胶质递质，这可能导致大脑过度兴奋的状态。由于REM睡眠的性质随着癫痫的发展而改变，REM睡眠分析可以作为癫痫发生严重程度的生物标志物。快速眼动睡眠分析也可以预测是否一个特定的快速眼动睡眠事件触发睡眠后癫痫发作。Ikoma等人报道了与快速眼动睡眠相关的小鼠外侧下丘脑星形胶质细胞Ca 2+、pH和脑血容量动力学的变化，并表明这些特性随着癫痫发生而改变。REM睡眠期间星形胶质细胞的pH值水平可以作为有利于神经元过度活跃的大脑环境的生物标志物。
It is usually assumed that individuals rest during sleep. However, coordinated neural activity that presumably requires high energy consumption is increased during REM sleep. Here, using freely moving male transgenic mice, the local brain environment and astrocyte activity during REM sleep were examined using the fibre photometry method with an optical fibre inserted deep into the lateral hypothalamus, a region that is linked with controlling sleep and metabolic state of the entire brain. Optical fluctuations of endogenous autofluorescence of the brain parenchyma or fluorescence of sensors for Ca2+ or pH expressed in astrocytes were examined. Using a newly devised method for analysis, changes in cytosolic Ca2+ and pH in astrocytes and changes in the local brain blood volume (BBV) were extracted. On REM sleep, astrocytic Ca2+ decreases, pH decreases (acidification) and BBV increases. Acidification was unexpected, as an increase in BBV would result in efficient carbon dioxide and/or lactate removal, which leads to alkalinization of the local brain environment. Acidification could be a result of increased glutamate transporter activity due to enhanced neuronal activity and/or aerobic metabolism in astrocytes. Notably, optical signal changes preceded the onset of the electrophysiological property signature of REM sleep by similar to 20-30 s. This suggests that changes in the local brain environment have strong control over the state of neuronal cell activity. With repeated stimulation of the hippocampus, seizure response gradually develops through kindling. After a fully kindled state was obtained with multiple days of stimuli, the optical properties of REM sleep at the lateral hypothalamus were examined again. Although a negative deflection of the detected optical signal was observed during REM sleep after kindling, the estimated component changed. The decrease in Ca2+ and increase in BBV were minimal, and a large decrease in pH (acidification) emerged. This acidic shift may trigger an additional gliotransmitter release from astrocytes, which could lead to a state of hyperexcitable brain. As the properties of REM sleep change with the development of epilepsy, REM sleep analysis may serve as a biomarker of epileptogenesis severity. REM sleep analysis may also predict whether a specific REM sleep episode triggers post-sleep seizures.Ikoma et al. report changes in astrocytic Ca2+, pH and brain blood volume dynamics in the mouse lateral hypothalamus in association with REM sleep, and show that these properties are altered with epileptogenesis. Astrocytic pH levels during REM sleep could serve as a biomarker for a brain environment favouring neuronal hyperactivity.