Lai Ren's team revealed that lipopolysaccharide/endotoxin-binding protein is an important factor in the inhibition of monoamine synthesis and the development of depression
Source：Mingqian Fang
2023-03-30
In March 2023, Lai Ren and his colleagues at Kunming Institute of Zoology, CAS in China published a research article in Immunity titled "Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms", found that inflammatory stress-dependent upregulation of lipopolysaccharide-binding protein (LBP) inhibits monoamine synthesis by interacting with dopamine decarboxylase (DDC) and dopamine β-hydroxylase (DBH). It may have an important regulatory role in the development of depression.
Major depressive disorder (MDD) is the leading cause of disability worldwide and is expected to become the leading cause of the global disease burden by 2030. The "monoamine hypothesis of depression" suggests that monoamine deficiency is an important factor in the development of depression, therefore, the pharmacological mechanism of current first-line antidepressants is mainly to inhibit monoamine degradation or prevent monoamine reabsorption, but about 50% of individuals with depression are non-responsive to these drugs. Indeed, long-term repeated treatment (several weeks or months) is often required before clinical improvement, indicating delayed pharmacological effects of antidepressants. These clinical phenomena suggest that the possible underlying pathology of some depressed individuals lies in the blocked synthesis of monoamines, and therefore the use of drugs that block monoamine degradation or reabsorption is ineffective.
Lai Ren's team found that chronic stress (e.g., social defeat stress, inflammatory stimuli, etc.) significantly inhibited the monoamine synthesis process and upregulated lipopolysaccharide/endotoxin binding protein (LBP) expression. LBP was significantly upregulated in depressed individuals. This research also identified LBP as an endogenous inhibitor of aromatic-L-amino-acid-decarboxylase (DDC) and dopamine-β-hydroxylase (DBH), key enzymes of monoamine synthesis, inhibiting monoamine synthesis, which may have an important role in the development of depression. In mouse models of depression, promising antidepressant therapeutic effects were shown by intervening in LBP-DDC/DBH interactions. These results reveal that the inhibition of monoamine synthesis by LBP is the underlying cause of low monoamine levels in some depressed individuals, and that LBP is an important molecule in mediating immune to-brain bidirectional communication, providing new targets and directions for future treatment and diagnosis of depression.
Prof. Ren Lai, Kunming Institute of Zoology, Chinese Academy of Sciences, is the corresponding author of this paper, and Dr. Mingqian Fang and M.S. Yu Li are the co-first authors; This study was greatly supported by Drs. Li Ya, Yong Duan, and Yanbing Han at the First Affiliated Hospital of Kunming Medical University.
Article Link: https://doi.org/10.1016/j.immuni.2023.02.002
Major depressive disorder (MDD) is the leading cause of disability worldwide and is expected to become the leading cause of the global disease burden by 2030. The "monoamine hypothesis of depression" suggests that monoamine deficiency is an important factor in the development of depression, therefore, the pharmacological mechanism of current first-line antidepressants is mainly to inhibit monoamine degradation or prevent monoamine reabsorption, but about 50% of individuals with depression are non-responsive to these drugs. Indeed, long-term repeated treatment (several weeks or months) is often required before clinical improvement, indicating delayed pharmacological effects of antidepressants. These clinical phenomena suggest that the possible underlying pathology of some depressed individuals lies in the blocked synthesis of monoamines, and therefore the use of drugs that block monoamine degradation or reabsorption is ineffective.
Lai Ren's team found that chronic stress (e.g., social defeat stress, inflammatory stimuli, etc.) significantly inhibited the monoamine synthesis process and upregulated lipopolysaccharide/endotoxin binding protein (LBP) expression. LBP was significantly upregulated in depressed individuals. This research also identified LBP as an endogenous inhibitor of aromatic-L-amino-acid-decarboxylase (DDC) and dopamine-β-hydroxylase (DBH), key enzymes of monoamine synthesis, inhibiting monoamine synthesis, which may have an important role in the development of depression. In mouse models of depression, promising antidepressant therapeutic effects were shown by intervening in LBP-DDC/DBH interactions. These results reveal that the inhibition of monoamine synthesis by LBP is the underlying cause of low monoamine levels in some depressed individuals, and that LBP is an important molecule in mediating immune to-brain bidirectional communication, providing new targets and directions for future treatment and diagnosis of depression.
Figure: Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms
Prof. Ren Lai, Kunming Institute of Zoology, Chinese Academy of Sciences, is the corresponding author of this paper, and Dr. Mingqian Fang and M.S. Yu Li are the co-first authors; This study was greatly supported by Drs. Li Ya, Yong Duan, and Yanbing Han at the First Affiliated Hospital of Kunming Medical University.
Article Link: https://doi.org/10.1016/j.immuni.2023.02.002
