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

WANG Min-Yuan¹, LI Jia-Mei^1,2, WU Yi¹, ZHANG Yi³, HU Ting¹, SU Wen-Jun¹, FENG Ji-Feng¹, JIANG Chun-Lei^1,*

¹Department of Stress Medicine, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai 200043, China；²Department of Neurology, Navy 971st Hospital of PLA, Qingdao 266071, China；³Department of Psychiatry, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai 200043, China

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.

Key words: aryl hydrocarbon receptor; NLRP3 inflammasome; IL-1β; IL-6; depression; inflammation

Received: 　　Accepted:

Corresponding author: 蒋春雷　　E-mail:

DOI: 10.13294/j.aps.2024.0031

Citing This Article：

WANG Min-Yuan, LI Jia-Mei, WU Yi, ZHANG Yi, HU Ting, SU Wen-Jun, FENG Ji-Feng, JIANG Chun-Lei. Activation of aryl hydrocarbon receptor (AhR) alleviates depressive- like behaviors in LPS-induced mice. Acta Physiol Sin 2024; 76 (3): 353-364