Related Experiment Video
Updated: Jan 18, 2026
Author Spotlight: Induced Microglia-Like Cell Technology to Shed Light on the Role of Microglial Dysfunction in Neuropsychiatric Disorders
Published on: September 6, 2024
Microglia contribute to bipolar depression through Serinc2-dependent phospholipid synthesis
Ying-Han Wang1, Chong-Lei Fu2, Lin-Bo Chen1
1State Key Laboratory of Membrane Biology, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Abstract:
Although clinical research has revealed microglia-related inflammatory and immune responses in bipolar disorder (BD) patient brains, it remains unclear how microglia contribute to the pathogenesis of BD. Here, we demonstrated that Serinc2 is associated with susceptibility to BD and showed a reduced expression in BDII patient plasma, which correlated with the disease severity. Using induced pluripotent stem cell (iPSC) models of sporadic and familial BDII patients, we found that Serinc2 expression showed deficits in iPSC-derived microglia-like cells, resulting in decreased synaptic pruning. Further, combining the microglia-specific Serinc2-deficient mouse and iPSC-microglia models, we found that microglial Serinc2 deficits functioned through attenuating the synthesis of serine-related phospholipids in the plasma membrane, thus resulting in depression-like behavioral abnormalities in the animals. Finally, we showed that the Serinc2-dependent lipid deficits diminished microglial membrane CR3 formation to interrupted synaptic pruning signals from neurons. Therefore, our results indicated that Serinc2 deficits in microglia might contribute to the pathogenesis of BD.
Insights
Serine-3 (Serinc2) deficits in microglia contribute to bipolar disorder (BD) by impairing synaptic pruning. Reduced Serinc2 expression in BDII patients correlates with disease severity, suggesting a potential therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia play a role in bipolar disorder (BD) pathogenesis through inflammatory and immune responses.
- The specific contribution of microglia to BD remains incompletely understood.
Purpose of the Study:
- To investigate the role of Serine-3 (Serinc2) in BD susceptibility and pathogenesis.
- To elucidate the mechanisms by which microglial Serinc2 influences BD-related behaviors.
Main Methods:
- Analysis of Serinc2 expression in BDII patient plasma.
- Utilized induced pluripotent stem cell (iPSC)-derived microglia-like cells from BDII patients.
- Generated microglia-specific Serinc2-deficient mouse models.
- Combined iPSC-microglia and mouse models to study Serinc2 function.
Main Results:
- Reduced Serinc2 expression was observed in BDII patient plasma and iPSC-derived microglia, correlating with disease severity.
- Microglial Serinc2 deficiency led to decreased synaptic pruning and depression-like behaviors in mice.
- Serinc2 deficits impaired serine-related phospholipid synthesis, affecting microglial membrane CR3 formation and synaptic pruning signals.
Conclusions:
- Microglial Serinc2 deficits are associated with BD susceptibility and pathogenesis.
- Impaired synaptic pruning due to Serinc2-dependent lipid alterations contributes to BD-related behavioral abnormalities.
- Serinc2 represents a potential target for understanding and treating BD.
