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  3. Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms

Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms

  • Immunity. 2023 Feb 22;S1074-7613(23)00073-0. doi: 10.1016/j.immuni.2023.02.002.
Mingqian Fang 1,  Yu Li 2,  Zhiyi Liao 3,  Gan Wang 1,  Qiqi Cao 1,  Ya Li 4,  Yong Duan 4,  Yanbing Han 4,  Xinyi Deng 1,  Feilong Wu 3,  Peter Muiruri Kamau 3,  Qiumin Lu 1,  Ren Lai 5
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Models and Human Disease Mechanisms and Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Institute, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
  • 2 Key Laboratory of Animal Models and Human Disease Mechanisms and Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Institute, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; College of Life Science, Zhengzhou University, Zhengzhou, Henan 450001, China.
  • 3 Key Laboratory of Animal Models and Human Disease Mechanisms and Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Institute, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
  • 5 Key Laboratory of Animal Models and Human Disease Mechanisms and Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), and Sino-African Joint Research Center, New Cornerstone Science Institute, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. Electronic address: rlai@mail.kiz.ac.cn.
PMID: 36854305 DOI: 10.1016/j.immuni.2023.02.002
Abstract

Monoamine insufficiency is suggested to be associated with depressive features such as sadness, anhedonia, 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-β-hydroxylase (DBH) and aromatic-L-amino-acid-decarboxylase (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 monoamine biosynthesis and suggests that targeting LBP may have potential as a treatment for some individuals with depression.

Keywords

LBP; depression; lipopolysaccharide-binding protein; monoamine insufficiency; monoamine pathway enzymes; stress.

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