Background Postoperative cognitive dysfunction (POCD) is a very common complication that might increase the morbidity and mortality of elderly patients after surgery. However, the mechanism of POCD remains largely unknown. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) is located in the mitochondria and regulates mitochondrial function. SIRT3 is the only sirtuin that specifically plays a role in extending lifespan in humans and is associated with neurodegenerative diseases. Therefore, the aim of this study was to evaluate the effect of SIRT3 on anesthesia/surgery-induced cognitive impairment in aged mice. Methods SIRT3 expression levels were decreased after surgery. For the interventional study, an adeno-associated virus (AAV)-SIRT3 vector or an empty vector was microinjected into hippocampal CA1 region before anesthesia/surgery. Western blotting, immunofluorescence staining, and enzyme-linked immune-sorbent assay (ELISA) were used to measure the oxidative stress response and downstream microglial activation and proinflammatory cytokines, and Golgi staining and long-term potentiation (LTP) recording were applied to evaluate synaptic plasticity. Results Overexpression of SIRT3 in the CA1 region attenuated anesthesia/surgery-induced learning and memory dysfunction as well as synaptic plasticity dysfunction and the oxidative stress response (superoxide dismutase [SOD] and malondialdehyde [MDA]) in aged mice with POCD. In addition, microglia activation (ionized calcium binding adapter molecule 1 [Iba1]) and neuroinflammatory cytokine levels (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β and IL-6) were regulated after anesthesia/surgery in a SIRT3-dependent manner. Conclusion The results of the current study demonstrate that SIRT3 has a critical effect in the mechanism of POCD in aged mice by suppressing hippocampal neuroinflammation and reveal that SIRT3 may be a promising therapeutic and diagnostic target for POCD.

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Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients. Circular RNAs (circRNAs) may contribute to neurodegenerative diseases. However, the role of circRNAs in POCD in aged mice has not yet been reported. This study aimed to explore the potential circRNAs in a POCD model. First, a circRNA microarray was used to analyze the expression profiles. Differentially expressed circRNAs were validated using quantitative real-time polymerase chain reaction. A bioinformatics analysis was then used to construct a competing endogenous RNA (ceRNA) network. The database for annotation, visualization, and integrated discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of circRNA-related genes. Moreover, protein-protein interactions were analyzed to predict the circRNA-regulated hub genes using the STRING and molecular complex detection plug-in of Cytoscape. Microarray screen 124 predicted circRNAs in the POCD of aged mice. We found that the up/downregulated circRNAs were involved in multiple signaling pathways. Hub genes, including Egfr and Prkacb, were identified and may be regulated by ceRNA networks. These results suggest that circRNAs are dysexpressed in the hippocampus and may contribute to POCD in aged mice.

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The mechanism by which general anesthetic drugs modify the state of consciousness remains unidenti ed. In essence, the Nucleus Accumbens(NAc)may be directly engaged in the principle of general anesthesia. However, it is uncertain whether NAc GABAergic neurons play a role in the propofol-induced general anesthesia effect. MethodsWe used immuno uorescence and Western blotting to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to investigate the necessity of NAc GABAergic neurons in the change of consciousness. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. ResultsWe found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. ConclusionsOur results demonstrate that NAc GABAergic neurons modulate induction and emergence of propofol anesthesia. | BackgroundGeneral anesthesia is a reversible condition of unconsciousness induced by anesthetic medications, which have been commonly used in clinical surgery for almost two hundred years [1]. Particularly, the mechanism by which general anesthetic drugs unleash the general anesthesia effect and ulteriorly modify the state of consciousness remains unidenti ed [2]. When general anesthetic drugs are applied for operations, patients frequently have adverse reactions such as low blood pressure, respiratory depression, delayed waking, and even death [3]. Additionally, cognitive dysfunction and stress disorder are likely to be continually companied by patients for a long period [4]. Unfortunately, few effective treatments exist for these debilitating illnesses, accounting for the uncertain mechanism of general anesthesia [2]. As a result,