Microglia modulate stable wakefulness via the thalamic reticular nucleus in mice.
Microglia modulate stable wakefulness via the thalamic reticular nucleus in mice.
复制标题
小胶质细胞通过丘脑网状核调节小鼠的稳定觉醒。
DOI：
10.1038/s41467-021-24915-x
复制
发表时间：
2021-07-30
影响因子：
16.6
通讯作者：
Xiong Q
中科院分区：
文献类型：
--
作者：
Liu H;Wang X;Chen L;Chen L;Tsirka SE;Ge S;Xiong Q
小胶质细胞对大脑的稳态和免疫很重要，但它们在调节警惕性方面的作用仍不清楚。我们采用遗传学、生理学和代谢组学的方法来研究小胶质细胞参与觉醒和睡眠的调节。小胶质细胞耗竭通过增加清醒和非快速眼动（NREM）睡眠之间的过渡来减少小鼠的稳定夜间觉醒。代谢组学分析显示，睡眠-觉醒行为与脑神经酰胺的昼夜变化密切相关，而在小胶质细胞耗竭的小鼠中，神经酰胺的昼夜变化消失。神经酰胺优先影响丘脑网状核（TRN）中的小胶质细胞，TRN小胶质细胞的局部耗竭产生类似的觉醒受损。前TRN神经元的化学发生操纵表明，它们调节觉醒和NREM睡眠之间的转换。它们的放电能力受到小胶质细胞耗竭和添加神经酰胺的抑制。在小胶质细胞耗尽的小鼠中，激活前TRN神经元或抑制神经酰胺的产生都恢复了稳定的觉醒。这些发现表明，小胶质细胞可以通过神经酰胺信号通过前TRN神经元调节稳定的觉醒。在这里，作者表明，小胶质细胞耗竭导致不稳定的觉醒和神经酰胺水平的改变，影响小鼠丘脑网状核（TRN）中的小胶质细胞。稳定的觉醒可以通过激活TRN或抑制小鼠大脑中神经酰胺的产生来恢复。
Microglia are important for brain homeostasis and immunity, but their role in regulating vigilance remains unclear. We employed genetic, physiological, and metabolomic methods to examine microglial involvement in the regulation of wakefulness and sleep. Microglial depletion decreased stable nighttime wakefulness in mice by increasing transitions between wakefulness and non-rapid eye movement (NREM) sleep. Metabolomic analysis revealed that the sleep-wake behavior closely correlated with diurnal variation of the brain ceramide, which disappeared in microglia-depleted mice. Ceramide preferentially influenced microglia in the thalamic reticular nucleus (TRN), and local depletion of TRN microglia produced similar impaired wakefulness. Chemogenetic manipulations of anterior TRN neurons showed that they regulated transitions between wakefulness and NREM sleep. Their firing capacity was suppressed by both microglial depletion and added ceramide. In microglia-depleted mice, activating anterior TRN neurons or inhibiting ceramide production both restored stable wakefulness. These findings demonstrate that microglia can modulate stable wakefulness through anterior TRN neurons via ceramide signaling. Here, the authors show that microglia depletion results in unstable wakefulness and altered levels of ceramide, influencing microglia in the mouse thalamic reticular nucleus (TRN). Stable wakefulness can be restored by activation of the TRN or inhibition of ceramide production in the mouse brain.
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DOI：
10.3233/jad-2011-111202
发表时间：
2012
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Filippov V;Song MA;Zhang K;Vinters HV;Tung S;Kirsch WM;Yang J;Duerksen-Hughes PJ
通讯作者：
Duerksen-Hughes PJ
影响因子：
4.2
作者：
Dinkins MB;Dasgupta S;Wang G;Zhu G;Bieberich E
通讯作者：
Bieberich E
影响因子：
3.5
作者：
Chen Z;Wimmer RD;Wilson MA;Halassa MM
通讯作者：
Halassa MM
一种用于飞行行为的新型皮质-丘脑内回路
影响因子：
25
作者：
Dong, Ping;Wang, Hao;Li, Xiao-Ming
通讯作者：
Li, Xiao-Ming
影响因子：
64.5
作者：
Halassa MM;Chen Z;Wimmer RD;Brunetti PM;Zhao S;Zikopoulos B;Wang F;Brown EN;Wilson MA
通讯作者：
Wilson MA