Lipopolysaccharide-binding Protein Expression is Increased by Stress and Inhibits Monoamine Synthesis to Promote Depressive Symptoms

author:	Fang, MQ (Fang, Mingqian); Li, Y (Li, Yu); Liao, ZY (Liao, Zhiyi); Wang, G (Wang, Gan); Cao, QQ (Cao, Qiqi); Li, Y (Li, Ya); Duan, Y (Duan, Yong); Han, YB (Han, Yanbing); Deng, XY (Deng, Xinyi); Wu, FL (Wu, Feilong); Kamau, PM (Kamau, Peter Muiruri); Lu, QM (Lu, Qiumin); Lai, R (Lai, Ren)
Abstract:	Monoamine insufficiency is suggested to be associated with depressive features such as sadness, anhe-donia, insomnia, and cognitive dysfunction, but the mechanisms that cause it are unclear. We found that the acute-phase protein lipopolysaccharide-binding protein (LBP) inhibits monoamine biosynthesis by acting as an endogenous inhibitor of dopamine-b-hydroxylase (DBH) and aromatic-L-amino-acid-decarbox-ylase (DDC). LBP expression was increased in individuals with depression and by diverse stress challenges in mice. LBP antibodies and LBP knockdown inhibited monoamine insufficiency and depression-like features in mice, which worsened with LBP overexpression or administration. Monoamine insufficiency and depression -like symptoms were not induced by stressful stimuli in LBP-deficient mice, further highlighting a role for LBP in stress-induced depression, and a peptide we designed that blocks LBP-DBH and LBP-DDC interactions showed anti-depression effects in mice. This study reveals an important role for LBP in regulating mono -amine biosynthesis and suggests that targeting LBP may have potential as a treatment for some individuals with depression
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PubYear:	2023
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Unit code:	152453
Publication name:	Immunity
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Paper source:	https://www.sciencedirect.com/science/article/pii/S1074761323000730?via%3Dihub
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