Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

Q3 Medicine
生理学报 Pub Date : 2024-06-25
Min-Yuan Wang, Jia-Mei Li, Yi-Lin Wu, Yi Zhang, Ting Hu, Wen-Jun Su, Ji-Feng Feng, Chun-Lei Jiang
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引用次数: 0

Abstract

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1β levels in the hippocampus, increased serum IL-1β level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

激活芳基烃受体(AhR)可减轻 LPS 诱导的小鼠的抑郁样行为。
人们越来越认识到芳基烃受体(AhR)在调节氧化应激和免疫反应中的作用。然而,人们对其在抑郁症中的参与及其内在机制仍知之甚少。本研究旨在探讨内源性 AhR 配体 6-甲酰基吲哚并[3,2-b]咔唑(FICZ)对脂多糖(LPS)诱导的抑郁模型的影响及其内在机制。雄性C57BL/6J小鼠经FICZ(50 mg/kg)治疗后腹腔注射LPS,24 h后进行行为测试。用酶联免疫吸附试验(ELISA)测定了海马和血清中的炎性细胞因子水平,包括IL-1β、IL-6和TNF-α。利用 qPCR 和 Western 印迹分析了 CYP1A1、AhR 和 NLRP3 的表达水平。结果表明,与对照组相比,LPS能显著下调小鼠海马中CYP1A1 mRNA和AhR蛋白的表达水平,降低葡萄糖偏好性,延长强迫游泳试验的不动时间,增加海马中IL-6和IL-1β的水平,提高血清中IL-1β的水平,上调小鼠海马中NLRP3 mRNA和蛋白的表达水平。这些研究结果表明,AhR激活可减轻抑郁症相关的炎症反应,并调节NLRP3的表达。本研究对 AhR 在抑郁症发病中的作用提供了新的见解,并将 AhR 作为治疗抑郁症的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
生理学报
生理学报 Medicine-Medicine (all)
CiteScore
1.20
自引率
0.00%
发文量
4820
期刊介绍: Acta Physiologica Sinica (APS) is sponsored by the Chinese Association for Physiological Sciences and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences (CAS), and is published bimonthly by the Science Press, China. APS publishes original research articles in the field of physiology as well as research contributions from other biomedical disciplines and proceedings of conferences and symposia of physiological sciences. Besides “Original Research Articles”, the journal also provides columns as “Brief Review”, “Rapid Communication”, “Experimental Technique”, and “Letter to the Editor”. Articles are published in either Chinese or English according to authors’ submission.
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