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

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General anesthesia severely affects the metabo-lites 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-l,4-imino-D-arabinitol(DAB),a GP antagonist,we found a prolonged time of emergence from anesthesia and an enhanced 8 frequency in the EEG(electroencephalogram).In addition,augmented expression of glycogenolysis genes in glycogen phosphorylase,brain(Pygb)knock-in(PygbH11/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.
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