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Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2024 Jul 30; Vol. 136, pp. 112330. Date of Electronic Publication: 2024 May 31. - Publication Year :
- 2024
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Abstract
- 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), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) 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 depressive-like 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-α, 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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Antidepressive Agents pharmacology
Antidepressive Agents therapeutic use
Disease Models, Animal
Behavior, Animal drug effects
Neuroinflammatory Diseases drug therapy
Neuroinflammatory Diseases immunology
Mice, Inbred C57BL
Inflammation Mediators metabolism
Microglia drug effects
Lipopolysaccharides
Hippocampus drug effects
Hippocampus metabolism
Hippocampus pathology
Depression drug therapy
Depression immunology
Depression chemically induced
Stress, Psychological drug therapy
Stress, Psychological immunology
Coumarins pharmacology
Coumarins therapeutic use
Cytokines metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 136
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38823180
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112330