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To investigate if glial cells infection could impair the function of neuronal networks, primary rat cortical cultures seeded on multi-electrode arrays were used to monitor the electrical activity after exposure to SARS-CoV-2. Effective SARS-CoV-2 infection of the glia led to a major loss of synaptic connections, an increase expression and production of pro-inflammatory cytokines and chemokines, and an increase of DNA damage foci. Intriguingly, the pro-inflammatory response was cGAS-STING dependent. Finally, an antagonist of the cGAS-STING pathway was able to ameliorate the decrease in electrical activity early post-infection. These data point to SARS-CoV-2 infection of the glia as a culprit for neurological complications during COVID-19.<\/jats:p>","DOI":"10.1007\/s13365-025-01283-6","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T18:02:08Z","timestamp":1761415328000},"page":"528-554","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SARS-CoV-2-induced damage to rat cortical neuronal networks ex vivo is mediated by the pro-inflammatory activation of the cGAS-STING pathway"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2025-9445","authenticated-orcid":false,"given":"Pamela","family":"Martinez-Orellana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-0088","authenticated-orcid":false,"given":"Matteo","family":"Manzati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-8050","authenticated-orcid":false,"given":"Diletta","family":"Pozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7216-0031","authenticated-orcid":false,"given":"Yingying","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7129-7882","authenticated-orcid":false,"given":"Alessio","family":"Di Clemente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5168-3130","authenticated-orcid":false,"given":"Marika","family":"Mearelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3523-7562","authenticated-orcid":false,"given":"Chiara","family":"Kalebi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9011-3671","authenticated-orcid":false,"given":"Valentina","family":"Perrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8961-6321","authenticated-orcid":false,"given":"Denise","family":"Ferrarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2510-2399","authenticated-orcid":false,"given":"Tea","family":"Carletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-1171","authenticated-orcid":false,"given":"Carmen","family":"Falcone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2626-594X","authenticated-orcid":false,"given":"Michele","family":"Giugliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8903-8202","authenticated-orcid":false,"given":"Alessandro","family":"Marcello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"1283_CR1","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nature12640","volume":"503","author":"A Ablasser","year":"2013","unstructured":"Ablasser A, Schmid-Burgk JL, Hemmerling I et al (2013) Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. 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