| 作者: |
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) |
| 摘要: |
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 |
