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The pathway induces type I interferon response and activates transcription of interferon\u2010stimulated genes and proinflammatory cytokines. Though the brain is an immune\u2010privileged site, the blood\u2013brain barrier (BBB) elicits inflammatory immune response in neurodegenerative diseases. Parkinson's disease is characterized by \u03b1\u2010synuclein oligomer (\u03b1SO) aggregates, neurodegeneration, and mitophagy, which potential can activate the cGAS\u2010STING pathway. Here, we studied the cGAS\u2010STING pathway in a co\u2010culture model of the rat BBB treated with and without \u03b1\u2010synuclein monomers (\u03b1SM) or oligomers (\u03b1SO). Activation of the cGAS\u2010STING pathway did not change barrier integrity and junctional protein staining, but it induced the transcription of the interferon\u2010stimulated gene Viperin and the proinflammatory cytokine tumor necrosis factor\u2010\u03b1 in brain endothelial cells. Furthermore, STING activation increased the protein level of Viperin in astrocytes. The treatment with \u03b1SO, but not \u03b1SM, decreased barrier tightness and induced the transcription of Viperin and tumor necrosis factor\u2010\u03b1 in brain endothelial cells. In astrocytes, \u03b1SO treatment increased not only Viperin and tumor necrosis factor\u2010\u03b1 mRNA levels, but also interleukin\u20101\u03b2 and interleukin\u20106. In conclusion, cGAS\u2010STING pathway and downstream immune signaling pathways can be activated in the cells of a co\u2010culture model of the BBB without influencing barrier integrity. However, \u03b1SO disrupts the BBB integrity and activates the cGAS\u2010STING immune pathway in brain endothelial cells and astrocytes supporting the idea of using cGAS\u2010STING as a therapeutic target in neuroinflammation.<\/jats:p>","DOI":"10.1002\/cbf.70240","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T08:18:11Z","timestamp":1780561091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Double\u2010Stranded DNA Sensing cGAS\u2010STING Immune Signaling in a Rat Co\u2010Culture Model of the Blood\u2013Brain Barrier"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-5606","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Harazin","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Faculty of Health Aarhus University  Aarhus Denmark"},{"name":"Department of Molecular Biology and Genetics, Faculty of 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