Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia

被引:3
作者
Zhang, Lu-wen [1 ]
Cui, Chun-ai [2 ]
Liu, Chao [3 ]
Sun, Lian-ping [4 ]
Ouyang, Yi-nan [4 ]
Li, Long-fei [1 ]
Zhang, Dong-liang [1 ]
Yu, Hai-ling [1 ]
机构
[1] Yanbian Univ, Coll Med, Dept Funct Sci, Pk St 977, Yanji 133002, Jilin, Peoples R China
[2] Yanbian Univ, Coll Med, Dept Anat, Yanji, Jilin, Peoples R China
[3] Yanbian Univ, Dept Neurol, Affiliated Hosp, Yanji, Jilin, Peoples R China
[4] Yanbian Univ, Coll Med, Dept Morphol Expt, Yanji, Jilin, Peoples R China
基金
中国国家自然科学基金;
关键词
Auraptene; Unpredictable chronic mild stress; Hippocampus; Neuroinflammation; Microglia; Mice; ROLES; MODEL;
D O I
10.1016/j.intimp.2024.112330
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive -like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive -like behavior. Cyclooxygenase-2 (COX -2), Creactive protein (CRP), tumor necrosis factor (TNF-alpha), interleukin-6 (IL -6), and interleukin-18 (IL -18) were examined by ELISA. Interleukin-10 (IL -10), interleukin-4 (IL -4), and transforming growth factor -8 (TGF-8) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressivelike behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro -inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro -cultured BV -2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL -6, TNF-alpha, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive -like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.
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页数:11
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