Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep-wake states
Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep-wake states
复制标题
小鼠皮质兴奋性神经元细胞内 ATP 水平随睡眠-觉醒状态变化
DOI：
10.1038/s42003-020-01215-6
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发表时间：
2020
影响因子：
5.9
通讯作者：
M. Honda
中科院分区：
文献类型：
--
作者：
A. Natsubori;T. Tsunematsu;A. Karashima;H. Imamura;N. Kabe;A. Trevisiol;J. Hirrlinger;T. Kodama;T. Sanagi;K. Masamoto;N. Takata;K-A Nave;K. Matsui;K.F. Tanaka;M. Honda
虽然大脑被认为在生理条件下发挥稳态功能以保持细胞能量状态恒定，但这尚未得到实验证明。在这里，我们使用小鼠大脑中的遗传编码传感器对细胞内主要细胞能量代谢物腺苷5 ' -三磷酸（ATP）的浓度进行了体内光学记录。我们证明，皮层兴奋性神经元的细胞内ATP水平在整个皮层范围内波动，这取决于睡眠-觉醒状态，与觉醒相关。有趣的是，在快速眼动睡眠期间，ATP水平急剧下降，这表明尽管大脑血流动力学的能量供应同时增加，但神经元的能量平衡为负。细胞内ATP的减少也被观察到响应局部电刺激神经元激活，而血流动力学同时增强。这些观察结果表明，脑能代谢可能并不总是满足神经元的能量需求，从而导致神经元细胞内ATP水平的生理波动。
Whilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons.