Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC
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槲皮素通过调节海马和 PFC 中与 BDNF 相关的 Copine 6 和 TREM1/2 失衡来减轻 LPS 诱导的大鼠抑郁样行为

DOI:
10.3389/fphar.2019.01544
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发表时间:
2020-01-17
影响因子:
5.6
通讯作者:
Ge, Jin-Fang
Ge, Jin-Fang
中科院分区:
医学2区
文献类型:
--
作者:
Fang, Ke;Li, Hua-Rong;Ge, Jin-Fang

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槲皮素是一种具有多种生物活性的多酚类化合物,我们的初步研究结果表明,槲皮素能缩短小鼠在强迫游泳实验和悬尾实验中的不动时间。本研究旨在观察其对脂多糖(LPS)攻击大鼠行为学的影响,并探讨其可能的作用机制。结果表明,槲皮素(40 mg/kg)灌胃可提高LPS攻击大鼠的体重增长,增加糖精偏爱实验中的糖精偏爱指数和Y迷宫中的新臂偏爱指数,减少FST中的不动时间。然而,它没有表现出显着的影响,在Morris水迷宫中的LPS攻击的大鼠的性能和nesfatin-1,C-反应蛋白(CRP)和IL-6的血浆浓度。蛋白质印迹结果显示,脂多糖攻击大鼠海马和前额叶皮质(PFC)中的脑源性神经营养因子(BDNF)、Copine 6、p-TrkB和髓样细胞表达的触发受体(TREM)1的表达水平下降,而TREM 2的表达则增加。海马突触素-1蛋白表达下降,而PFC无明显变化,槲皮素可平衡这些不平衡的蛋白表达。结果提示,槲皮素可减轻LPS诱导的大鼠抑郁样行为和学习记忆障碍,其机制可能与调节海马和PFC中与BDNF相关的Copine 6和TREM 1/2表达失衡有关。
Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.