STING Mediates Microglial Polarization to Promote Neuroinflammation in Epilepsy-Related Cognitive Dysfunction - PubMed
6 hours ago
- #STING Pathway
- #Neuroinflammation
- #Cognitive Dysfunction
- Epilepsy often involves cognitive deficits, and neuroinflammation driven by microglia plays a key role in this process.
- The STING pathway, which responds to cytosolic double-stranded DNA, is activated following status epilepticus (SE) and peaks in expression on day 7, correlating with increased neuroinflammation.
- Activation of STING promotes a shift in microglia towards a pro-inflammatory M1 phenotype, mediated through the TBK1/NF-κB signaling axis, leading to the release of inflammatory cytokines like IL-6, IL-1β, and TNF-α.
- Inhibition of STING with C-176 reduces neuroinflammation, decreases M1 microglial polarization, increases anti-inflammatory M2 markers, and mitigates neuronal damage in SE-induced rats.
- Treatment with C-176 improves cognitive function, as evidenced by enhanced performance in the Morris water maze test, suggesting STING as a promising therapeutic target for epilepsy-related cognitive dysfunction.