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

Neuroscience Bulletin 2020年第12期36卷 1513-1523页

作者： Ze Fan Zhihao Zhang Shiyi Zhao Yuanyuan Zhu Dong Guo Bo Yang Lixia Zhuo Jiao Han Rui Wang Zongping Fang Hailong Dong Yan Li Lize Xiong Department of Anesthesiology and Perioperative Medicine Xijing HospitalFourth Military Medical UniversityXi'an 710032ShaanxiChina College of Basic Medicine Fourth Military Medical UniversityXi'an 710032ShaanxiChina Department of Neurobiology Fourth Military Medical UniversityXi'an 710032ShaanxiChina Center for Brain Science and Department of Anesthesiology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi*an 710061ShaanxiChina Translational Research Institute of Brain and Brain-Like Intelligence Department of Anesthesiology and Perioperative MedicineShanghai Fourth People's Hospital Affiliated to Tongji University School of MedicineShanghai 200081China

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-Darabinitol(DAB),a GP antagonist,we found a prolonged time of emergence from anesthesia and an enhancedδfrequency 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 anesthesiaarousal,providing a potential target for modulating anesthesia.

关键词： Anesthesia-arousal Brain glycogen General anesthesia glycogen phosphorylase glycogen synthetase Isoflurane

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