STING inhibition suppresses microglia-mediated synapses engulfment and alleviates motor functional deficits after stroke
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · cited 1× · see citing works
“The increased synapse elimination by microglia has also been reported in various brain diseases, such as Alzheimer’s disease [7–9], schizophrenia [10], neuropsychiatric lupus [11], depression [12], and sepsis-associated encephalopathy [13], and is intimately involved in disease progression.”
BackgroundMolecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052 · see citing works
Plasticity during stroke recovery: from synapse to behaviour
Murphy, T. H., & Corbett, D. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2735 · Cited by 1,938 · see citing works
cGAS–STING drives ageing-related inflammation and neurodegeneration
Gulen, M. F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, V. V., Favre, L., Mangeat, B., Kroese, L. J., et al. (2023) · Nature · doi:10.1038/s41586-023-06373-1 · Cited by 1,074 · cited 1× · see citing works
“…as Alzheimer’s disease [25, 26], Parkinson’s disease [27, 28], multiple sclerosis [29], neuropathic pain [30], ageing-related neurodegeneration [31], subarachnoid hemorrhage [32], and traumatic brain injury [33, 34], the regulatory role of STING in microglia-released inflammatory mediators has…”
BackgroundLiao, Y., Cheng, J., Kong, X., Li, S., Li, X., Zhang, M., Zhang, H., Yang, T., Dong, Y., Li, J., et al. (2020) · Theranostics · doi:10.7150/thno.47651 · Cited by 348 · see citing works
Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice
Xie, X., Ma, G., Li, X., Zhao, J., Zhao, Z., & Zeng, J. (2023) · Nature Aging · doi:10.1038/s43587-022-00337-2 · Cited by 292 · see citing works
Beyond Activation: Characterizing Microglial Functional Phenotypes
Lier, J., Streit, W. J., & Bechmann, I. (2021) · Cells · doi:10.3390/cells10092236 · Cited by 274 · cited 1× · see citing works
“3A), which is considered as a marker for microglia pro-inflammatory activation [39–42].”
BackgroundTau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation
Jin, M., Shiwaku, H., Tanaka, H., Obita, T., Ohuchi, S., Yoshioka, Y., Jin, X., Kondo, K., Fujita, K., Homma, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26851-2 · Cited by 223 · see citing works
Chung, H.-Y., Wickel, J., Hahn, N., Mein, N., Schwarzbrunn, M., Koch, P., Ceanga, M., Haselmann, H., Baade-Büttner, C., von Stackelberg, N., et al. (2023) · Science Advances · doi:10.1126/sciadv.abq7806 · Cited by 156 · see citing works
Szego, E. M., Malz, L., Bernhardt, N., Rösen-Wolff, A., Falkenburger, B. H., & Luksch, H. (2022) · eLife · doi:10.7554/elife.81943 · Cited by 94 · see citing works
Flagged first, then by citations
- Authors
- Wu, C., Zhang, S., Sun, H., Li, A., Hou, F., Qi, L., & Liao, H.
- Venue
- Journal of Neuroinflammation
- Published
- 2024-04-08
- Volume
- 21
- Issue
- 1
- ISSN
- 1742-2094
- Cited by
- 53
- References
- 10
- Language
- en
- Funders
- National Natural Science Foundation of China (82073831)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
