Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00587-3) contains supplementary material, which is available to authorized users.