SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus
SIRT1 Mediates Apelin-13 in Ameliorating Chronic Normobaric Hypoxia-induced Anxiety-like Behavior by Suppressing NF-κB Pathway in Mice Hippocampus
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DOI：
10.1016/j.neuroscience.2018.04.013
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发表时间：
2018-06-15
期刊：
影响因子：
3.3
通讯作者：
Gong, Yongsheng
中科院分区：
文献类型：
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作者：
Fan, Junming;Guang, Hui;Gong, Yongsheng
我们以前发现apelin-13改善慢性常压缺氧（CNH）诱导的小鼠焦虑样行为，但其机制尚不清楚。本研究旨在研究SIRT 1是否参与apelin-13在CNH处理的小鼠中的抗焦虑作用，并阐明潜在的潜在机制。我们发现apelin-13治疗逆转了CNH治疗小鼠海马中SIRT 1的减少和乙酰化p65（赖氨酸310）蛋白表达的增加，表明apelin-13通过激活SIRT 1抑制NF-κ B B信号通路。在行为学上，apelin-13改善CNH诱导的焦虑样行为，EX-527阻断apelin-13的有益作用，并且CNH的致焦虑作用被白藜芦醇预处理减弱，表明SIRT 1参与apelin-13对抗小鼠CNH诱导的焦虑样行为的作用。我们还发现，白藜芦醇治疗降低海马中IL-1 β，IL-6，TNF-α，PCNA，Bcl-2和乙酰基-p65水平，但增加Bax和caspase 3水平，表明白藜芦醇对细胞神经炎症和增殖具有抑制作用，同时对海马中小胶质细胞的凋亡具有促进作用。最后，通过PDTC阻断NF-κ B活性减少了CNH诱导的焦虑样行为，表明NF-κ B参与了小鼠CNH诱导的焦虑样行为。总之，本研究提供了SIRT 1通过抑制NF-κ B通路介导apelin-13在CNH处理的小鼠中的抗焦虑作用的第一个证据。这些结果暗示海马中apelin-SIRT 1-NF-κ B轴的功能障碍代表了导致神经炎症诱导和神经保护减少的潜在机制，从而在CNH处理的小鼠中诱导焦虑样行为。(C)2018年IBRO。由爱思唯尔有限公司发布。保留所有权利。
We previously showed that apelin-13 ameliorates chronic normobaric hypoxia (CNH)-induced anxietylike behavior in mice, the mechanism, however, is not well known. This study aims to investigate whether SIRT1 is involved in the anxiolytic effect of apelin-13 in CNH-treated mice, and to illustrate the potential underlying mechanism. We showed that apelin-13 treatment reversed a decrease in SIRT1 and an increase in acetylated p65 (lysine 310) proteins' expression in hippocampus of CNH-treated mice, indicating that apelin-13 inhibited NF-kappa B signaling pathway by activating SIRT1. Behaviorally, apelin-13 ameliorated CNH-induced anxiety-like behavior, EX-527 blocked the beneficial effect of apelin-13, and the anxiogenic effect of CNH was attenuated by resveratrol pretreatment, suggesting that SIRT1 was involved in the effect of apelin-13 against CNH-induced anxiety-like behavior in mice. We also showed that resveratrol treatment decreased IL-1 beta, IL-6, TNF-alpha, PCNA, Bcl-2, and acetyl-p65 levels, but increased Bax and caspase 3 levels in hippocampus, suggesting a suppressive effect of resveratrol on cellular neuroinflammation and proliferation while a promotive effect on apoptosis of microglia in hippocampus. Finally, blockade of NF-kappa B activity by PDTC diminished CNH-induced anxiety-like behavior, indicating that NF-kappa B was involved in CNH-induced anxiety-like behavior in mice. In conclusion, this study provides the first evidence that SIRT1 mediates the anxiolytic effect of apelin-13 in CNH-treated mice through the inhibition of NF-kappa B pathway. These results imply that dysfunction of the apelin-SIRT1-NF-kappa B axis in hippocampus represents a potential mechanism that results in the induction of neuroinflammation and reduction in neuroprotection, thus induces anxiety-like behavior in CNH-treated mice. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.