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Updated: Jun 29, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
STING inhibition suppresses microglia-mediated synapses engulfment and alleviates motor functional deficits after
Chaoran Wu1, Shiwen Zhang1, Hao Sun1
1New Drug Screening Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
Abstract:
Ischemic stroke is the leading cause of adult disability. Ischemia leads to progressive neuronal death and synapse loss. The engulfment of stressed synapses by microglia further contributes to the disruption of the surviving neuronal network and related brain function. Unfortunately, there is currently no effective target for suppressing the microglia-mediated synapse engulfment. Stimulator of interferon genes (STING) is an important participant in innate immune response. In the brain, microglia are the primary cell type that mediate immune response after brain insult. The intimate relationship between STING and microglia-mediated neuroinflammation has been gradually established. However, whether STING affects other functions of microglia remains elusive. In this study, we found that STING regulated microglial phagocytosis of synapses after photothrombotic stroke. The treatment of STING inhibitor H151 significantly improved the behavioral performance of injured mice in grid-walking test, cylinder test, and adhesive removal test after stroke. Moreover, the puncta number of engulfed SYP or PSD95 in microglia was reduced after consecutive H151 administration. Further analysis showed that the mRNA levels of several complement components and phagocytotic receptors were decreased after STING inhibition. Transcriptional factor STAT1 is known for regulating most of the decreased molecules. After STING inhibition, the nucleus translocation of phosphorylated STAT1 was also suppressed in microglia. Our data uncovered the novel regulatory effects of STING in microglial phagocytosis after stroke, and further emphasized STING as a potential drug-able target for post-stroke functional recovery.
Insights
Stimulator of interferon genes (STING) inhibition reduces microglial synapse engulfment after stroke. This novel finding offers a potential therapeutic target for improving functional recovery following ischemic stroke.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Ischemic stroke causes significant adult disability through neuronal death and synapse loss.
- Microglia-mediated synapse engulfment exacerbates neuronal network disruption post-stroke.
- The role of Stimulator of Interferon Genes (STING) in microglial function beyond neuroinflammation is not well understood.
Purpose of the Study:
- To investigate the role of STING in microglial phagocytosis of synapses after ischemic stroke.
- To evaluate the therapeutic potential of targeting STING for functional recovery post-stroke.
Main Methods:
- Photothrombotic stroke model in mice.
- Administration of STING inhibitor H151.
- Behavioral tests (grid-walking, cylinder, adhesive removal).
- Immunohistochemistry to quantify synapse engulfment (SYP, PSD95).
- Analysis of mRNA levels for complement components and phagocytic receptors.
- Assessment of STAT1 phosphorylation and nuclear translocation.
Main Results:
- STING inhibition with H151 significantly improved behavioral performance in stroke mice.
- H151 treatment reduced the engulfment of synapses (SYP, PSD95) by microglia.
- STING inhibition decreased mRNA levels of complement components and phagocytic receptors.
- Suppression of phosphorylated STAT1 nuclear translocation was observed after STING inhibition.
Conclusions:
- STING plays a novel regulatory role in microglial synapse phagocytosis following ischemic stroke.
- Inhibiting STING presents a potential therapeutic strategy for enhancing post-stroke functional recovery.
