General anesthesia severely affects the metabolites in the brain. Glycogen, principally stored in astrocytes and providing the short-term delivery of substrates to neurons, has been implicated as an affected molecule. However, whether glycogen plays a pivotal role in modulating anesthesia–arousal remains unclear. Here, we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions. Glycogen synthase (GS) and glycogen phosphorylase (GP), key enzymes of glycogen metabolism, showed increased activity after isoflurane exposure. Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), a GP antagonist, we found a prolonged time of emergence from anesthesia and an enhanced δ frequency in the EEG (electroencephalogram). In addition, augmented expression of glycogenolysis genes in glycogen phosphorylase, brain (Pygb) knock-in (Pygb^H11/H11) mice resulted in delayed induction of anesthesia, a shortened emergence time, and a lower ratio of EEG-δ. Our findings revealed a role of brain glycogen in regulating anesthesia–arousal, providing a potential target for modulating anesthesia.

全身麻醉严重影响大脑中的代谢产物。糖原主要存储在星形胶质细胞中，并提供底物向神经元的短期递送，已经被认为是一种受影响的分子。但是，糖原是否在调节麻醉-麻醉中起关键作用尚不清楚。在这里，我们证明了异氟烷麻醉的小鼠在大脑各个区域的糖原水平表现出动态变化。糖原代谢的关键酶糖原合酶（GS）和糖原磷酸化酶（GP）在异氟烷暴露后显示出增加的活性。用GP拮抗剂1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇（DAB）阻断糖原分解后，我们发现麻醉后的出苗时间延长，脑电图的δ频率增加（脑电图）。此外，^{H11 / H11}）小鼠导致麻醉诱导延迟，出现时间缩短和EEG-δ比率降低。我们的发现揭示了脑糖原在调节麻醉-麻醉中的作用，为调节麻醉提供了潜在的靶点。