Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice
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ORIGINAL ARTICLE
Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice Ze Fan1 • Zhihao Zhang2 • Shiyi Zhao1 • Yuanyuan Zhu3 • Dong Guo2 Bo Yang1 • Lixia Zhuo4 • Jiao Han4 • Rui Wang3 • Zongping Fang1 • Hailong Dong1 • Yan Li4 • Lize Xiong1,5
•
Received: 23 December 2019 / Accepted: 20 May 2020 Ó The Author(s) 2020
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
Ze Fan, Zhihao Zhang and Shiyi Zhao have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00587-3) contains supplementary material, which is available to authorized users. & Yan Li [email protected] & Lize Xiong [email protected]; [email protected] 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
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 enhanced d 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-d. 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
Introduction General anesthetics are widely used clinically. However, the mechanisms through which general anesthetics induce quiescent neuronal activity and cause unconsciousness remain largely unknown [1–6]. In recent decades, the role of cerebral energy metabolism has attracted increasi
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