Hippocampal FXR plays a role in the pathogenesis of depression: A preliminary study based on lentiviral gene modulation. (June 2018)

• Record Type: Journal Article
• Authors: Chen, Wei-Guan; Zheng, Jia-Xuan; Xu, Xi; Hu, Yu-Ming; Ma, Yu-Min
• Is Part Of: Psychiatry research. Volume 264(2018)
• Page Start: 374
• Page End: 379
• Publication Date: 2018-06
• Subjects: Brain-derived neurotrophic factor -- Depression -- Farnesoid X receptor -- Hippocampus; ANOVA analysis of variance -- BDNF brain derived neurotrophic factor -- CREB cAMP response element-binding protein -- CRTC2 CREB regulated transcription coactivator 2 -- CUMS chronic unpredictable mild stress -- FXR Farnesoid X receptor -- FST forced swimming test -- mPFC medial prefrontal cortex -- qRT-PCR quantitative real-time reverse transcription PCR -- SPT sucrose preference test -- TST tail suspension test; Psychiatry -- Periodicals; Psychiatry -- periodicals; Psychiatrie -- Périodiques; 616.89
• DOI: 10.1016/j.psychres.2018.04.025
• Languages: English
• ISSNs: 0165-1781

Abstract

Highlights: CUMS significantly enhanced the expression of FXR in hippocampus. Overexpression of hippocampal FXR induced depressive-like behaviors and decreased hippocampal BDNF expression in rats. Knockdown of hippocampal FXR prevented the CUMS-induced depressive-like behaviors and decreased hippocampal BDNF expression in rats. Abstract: As a well-known bile acid receptor, the role of Farnesoid X receptor (FXR) in the digestive system and cardiovascular system has been widely explored. However, there are very few studies involving FXR in the central nervous system. In this study, we explored the role of FXR in the pathogenesis of depression, a serious and worldwide neuropsychiatric disease. It was found that chronic unpredictable mild stress (CUMS) fully enhanced the protein and mRNA expressions of FXR in hippocampus, but not medial prefrontal cortex (mPFC). Overexpression of hippocampal FXR induced notable depressive-like behaviors and decreased expression of brain-derived neurotrophic factor (BDNF) in naïve rats, while knockdown of hippocampal FXR fully prevented the effects of CUMS on rat behaviors and hippocampal BDNF expression. Taken together, our research extends the knowledge of FXR's role in the central nervous system, and may provide a potential and novel therapeutic target for treating depression.