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星形胶质细胞的化学遗传激活以脑区依赖的方式调节睡眠-觉醒状态。

Chemogenetic activation of astrocytes modulates sleep-wakefulness states in a brain region-dependent manner.

作者信息

Kurogi Yuta, Sanagi Tomomi, Ono Daisuke, Tsunematsu Tomomi

机构信息

Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Department of Biological Sciences, Faculty of Science, Hokkaido University, Sapporo, Japan.

出版信息

Sleep Adv. 2024 Dec 17;5(1):zpae091. doi: 10.1093/sleepadvances/zpae091. eCollection 2024.

Abstract

STUDY OBJECTIVES

Astrocytes change their intracellular calcium (Ca) concentration during sleep/wakefulness states in mice. Furthermore, the Ca dynamics in astrocytes vary depending on the brain region. However, it remains unclear whether alterations in astrocyte activity can affect sleep-wake states and cortical oscillations in a brain region-dependent manner.

METHODS

Astrocyte activity was artificially manipulated in mice using chemogenetics. Astrocytes in the hippocampus and pons, which are 2 brain regions previously classified into different clusters based on their Ca dynamics during sleep-wakefulness, were focused on to compare whether there are differences in the effects of astrocytes from different brain regions.

RESULTS

The chemogenetic activation of astrocytes in the hippocampus significantly decreased the total time of wakefulness and increased the total time of sleep. This had little effect on cortical oscillations in all sleep-wakefulness states. On the other hand, the activation of astrocytes in the pons substantially suppressed rapid eye movement (REM) sleep in association with a decreased number of REM episodes, indicating strong inhibition of REM onset. Regarding cortical oscillations, the delta wave component during non-REM sleep was significantly enhanced.

CONCLUSIONS

These results suggest that astrocytes modulate sleep-wakefulness states and cortical oscillations. Furthermore, the role of astrocytes in sleep-wakefulness states appears to vary among brain regions.

摘要

研究目的

在小鼠的睡眠/觉醒状态期间,星形胶质细胞会改变其细胞内钙(Ca)浓度。此外,星形胶质细胞中的钙动力学因脑区而异。然而,尚不清楚星形胶质细胞活性的改变是否会以脑区依赖的方式影响睡眠-觉醒状态和皮层振荡。

方法

在小鼠中使用化学遗传学人工操纵星形胶质细胞活性。海马体和脑桥中的星形胶质细胞是先前根据其在睡眠-觉醒期间的钙动力学被分类为不同簇的两个脑区,重点比较来自不同脑区的星形胶质细胞在作用上是否存在差异。

结果

海马体中星形胶质细胞的化学遗传学激活显著减少了清醒总时长,并增加了睡眠总时长。这对所有睡眠-觉醒状态下的皮层振荡影响很小。另一方面,脑桥中星形胶质细胞的激活与快速眼动(REM)睡眠次数减少相关,显著抑制了REM睡眠,表明对REM起始有强烈抑制作用。关于皮层振荡,非REM睡眠期间的δ波成分显著增强。

结论

这些结果表明星形胶质细胞调节睡眠-觉醒状态和皮层振荡。此外,星形胶质细胞在睡眠-觉醒状态中的作用在不同脑区似乎有所不同。

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