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.
Highlights
Emerging evidence has indicated that a reduction in cellular adenosine triphosphate (ATP) levels is associated with a delay in isoflurane-induced loss of the righting reflex (LORR) in mice [13], suggesting that changes in available cerebral energy might regulate anesthetic effects [11,12,13]
Consistent with these data, the glycogen assay kit revealed higher glycogen levels in the homogenates of the CTX, HIPPO, THAL, and STRIAT after 2 h of isoflurane exposure (Fig. 1C). These data suggested that isoflurane anesthesia increases the glycogen levels in various brain regions, including the CTX, HIPPO, THAL, and STRIAT
We demonstrated that exposure to the inhalational anesthetic isoflurane increased the levels of glycogen in various brain regions: the CTX, HIPPO, THAL, and STRIAT
Summary
The mechanisms through which general anesthetics induce quiescent neuronal activity and cause unconsciousness remain largely unknown [1,2,3,4,5,6]. The role of cerebral energy metabolism has attracted increasing attention [7, 8]. Emerging evidence has indicated that a reduction in cellular adenosine triphosphate (ATP) levels is associated with a delay in isoflurane-induced loss of the righting reflex (LORR) in mice [13], suggesting that changes in available cerebral energy might regulate anesthetic effects [11,12,13].
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