Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-Ku, Tokyo, 156-8506, Japan.
Super-network Brain Physiology, Graduate School of Life Sciences, Tohoku University, Sendai, 980-8578, Japan.
Commun Biol. 2020 Sep 7;3(1):491. doi: 10.1038/s42003-020-01215-6.
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.
虽然人们认为大脑在生理条件下发挥着维持细胞能量状态稳定的自稳功能，但这尚未得到实验证实。在这里，我们使用小鼠大脑中的基因编码传感器进行了活体内的细胞内三磷酸腺苷（ATP）浓度的光学记录，ATP 是主要的细胞能量代谢物。我们证明，皮质兴奋性神经元的细胞内 ATP 水平根据睡眠-觉醒状态在皮质范围内波动，与觉醒相关。有趣的是，ATP 水平在快速眼动睡眠期间显著降低，这表明尽管脑血流动力学同时增加以供应能量，但神经元的能量平衡呈负值。局部电刺激激活神经元时也观察到细胞内 ATP 的减少，而同时血流动力学增强。这些观察结果表明，大脑能量代谢可能并不总是满足神经元的能量需求，因此导致神经元细胞内 ATP 水平的生理波动。
