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Updated: Jun 28, 2025
A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosis of synapses in a mouse model of
Qiu-Qin Han1, Shi-Yu Shen2, Ling-Feng Liang3
1Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China.
Background:
Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear.
Methods:
We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice.
Results:
LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice.
Conclusions:
The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.
Insights
Depression involves synaptic loss driven by microglia. Targeting the C1q/C3-CR3 complement pathway with a neutralizing antibody reduced this synaptic loss and improved depressive behaviors in a mouse model.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Synaptic loss is observed in depression.
- Activated microglia may contribute to synaptic loss and behavioral deficits.
- Mechanisms of microglial-synaptic interaction in depression are not fully understood.
Purpose of the Study:
- To investigate the role of microglial phagocytosis and the C1q/C3-CR3 complement pathway in a mouse model of depression.
- To evaluate the therapeutic potential of inhibiting this pathway.
Main Methods:
- Lipopolysaccharide (LPS) induced a depression mouse model.
- Assessed behaviors, synaptic integrity, microglial activity, and phagocytosis.
- Utilized a C1q neutralizing antibody to inhibit the C1q/C3-CR3 pathway.
Main Results:
- LPS induced depressive behaviors, synaptic loss, and abnormal microglial phagocytosis in the hippocampus.
- The C1q/C3-CR3 pathway was implicated in these changes.
- C1q antibody treatment reduced abnormal phagocytosis, synaptic loss, and improved behaviors.
Conclusions:
- The C1q/C3-CR3 complement pathway mediates abnormal microglial phagocytosis of synapses in depression.
- This pathway represents a potential therapeutic target for depression.
