Affiliation:
1. Department of Neurology, Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou China
2. Nanhai Translational Innovation Center of Precision Immunology Sun Yat‐Sen Memorial Hospital Foshan China
3. Shenshan Medical Center, Sun Yat‐sen Memorial Hospital Sun Yat‐sen University Shanwei China
4. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Guangzhou China
Abstract
AbstractAimsChronic alcohol exposure leads to persistent neurological disorders, which are mainly attributed to neuroinflammation and apoptosis. Stimulator of IFN genes (STING) is essential in the cytosolic DNA sensing pathway and is involved in inflammation and cellular death processes. This study was to examine the expression pattern and biological functions of STING signaling in alcohol use disorder (AUD).MethodsCell‐free DNA was extracted from human and mouse plasma. C57BL/6J mice were given alcohol by gavage for 28 days, and behavior tests were used to determine their mood and cognition. Cultured cells were treated with ethanol for 24 hours. The STING agonist DMXAA, STING inhibitor C‐176, and STING‐siRNA were used to intervene the STING. qPCR, western blot, and immunofluorescence staining were used to assess STING signaling, inflammation, and apoptosis.ResultsCirculating cell‐free mitochondrial DNA (mtDNA) was increased in individuals with AUD and mice chronically exposed to alcohol. Upregulation of STING signaling under alcohol exposure led to inflammatory responses in BV2 cells and mitochondrial apoptosis in PC12 cells. DMXAA exacerbated alcohol‐induced cognitive impairment and increased the activation of microglia, neuroinflammation, and apoptosis in the medial prefrontal cortex (mPFC), while C‐176 exerted neuroprotection.ConclusionActivation of STING signaling played an essential role in alcohol‐induced inflammation and mitochondrial apoptosis in the mPFC. This study identifies STING as a promising therapeutic target for AUD.
Funder
National Key Research and Development Program of China
Cited by
2 articles.
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