• Wenqing Gong, Shanshan Zhang, Ying Zong, Michael Halim, Zhonggan Ren, Yalin Wang, Yuanyuan Ma, Bing Li, Lixiang Ma, Guomin Zhou, Jin Yu, Junhai Zhang, and Qiong Liu.
• Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: 14211010033@fudan.edu.cn.
• J Affect Disord. 2019 Jul 1; 254: 15-25.

BackgroundDepression has recently been referred to as a neuroimmune disease because it is characterized by inflammatory changes in the cerebral cortex and hippocampus. Studies have demonstrated that microglial activation plays a crucial role in releasing inflammatory cytokines in the central nervous system (CNS), thereby contributing to depression, the mechanism underlying which remains unclear.MethodsFirst, we examined microglial activation and inflammatory changes in C57BL/6 male mice injected with lipopolysaccharide (LPS; 1 mg/kg), which leads to depressive behaviors in mice that were attenuated by the antidepressant clomipramine. Second, we utilized a BV2 cell line and primary microglial cultures to determine the inflammatory response in vitro, and the effects of clomipramine exerted on the inflammatory response using real-time polymerase chain reaction and ELISA. Third, we utilized NLRP3 (NOD-like receptor protein 3) knock-out (KO) mice to prove that NLRP3 is involved in the effects of clomipramine.ResultsThe results showed that LPS injection induced depressive-like behaviors in mice, as assessed using several behavioral tests including body weight, and forced swimming and tail suspension tests. The LPS-induced expression of interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor alpha could be downregulated by clomipramine pre-treatment both in vivo and in vitro. The inhibitory effect of clomipramine on the LPS-induced increase in cytokines was found at both the protein and gene levels. Clomipramine significantly reduced the LPS-induced increase in NLRP3 gene expression in BV2 cells. Furthermore, we utilized NLRP3 KO mice to explore whether NLPP3 was involved in this process and found that clomipramine treatment inhibits the LPS-induced increased expression of IL-1β.ConclusionThese results imply that clomipramine could attenuate depressive behaviors and neuroinflammation induced by LPS via partial regulation of NLRP3.Copyright © 2019 Elsevier B.V. All rights reserved.

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