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

Ze Fan 1• Zhihao Zhang 2• Shiyi Zhao 1• Yuanyuan Zhu 3• Dong Guo 2•Bo Yang 1• Lixia Zhuo 4
• Jiao Han 4• Rui Wang 3• Zongping Fang 1•Hailong Dong 1• Yan Li 4• Lize Xiong 1,5


1 Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
2 College of Basic Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
3 Department of Neurobiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
4 Center for Brain Science and Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
5 Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital Affiliated
to Tongji University School of Medicine, Shanghai 200081,China

Abstract

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 (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.

Keywords

Anesthesia-arousal;  Brain glycogen;  General anesthesia;  Glycogen phosphorylase;  Glycogen synthetase; Isoflurane

[SpringerLink]

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