{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:42:53Z","timestamp":1791855773617,"version":"4.3.4"},"reference-count":16,"publisher":"IMR Press","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Objective:This study aimed to determine whether activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway within hippocampal microglia contributes to postoperative cognitive dysfunction (POCD) in a diabetic mouse model. Diabetes was induced using a high-fat, high-sugar (HFHS) diet combined with streptozotocin (STZ).Methods:Diabetes was induced in C57BL\/6J mice using an HFHS diet followed by STZ. POCD was modeled via tibial fracture surgery under general anesthesia. Cognitive function was assessed using the Open Field Test, Y-maze, and contextual fear conditioning. cGAS-STING pathway activation was evaluated by western blot for cGAS and STING expression. Microglial activation was assessed by co-localization of Iba-1 and CD68 by immunofluorescence, and the co-localization of STING with Iba-1 in the hippocampus was examined by immunofluorescence. Hippocampal neuroinflammation was quantified by enzyme-linked immunosorbent assay (ELISA) for interleukin-1beta (IL-1\u03b2) and tumor necrosis factor-alpha (TNF-\u03b1). Neuronal injury and apoptosis were evaluated by Nissl staining and western blot for cleaved caspase-3.Results:Compared to non-diabetic controls, diabetic mice exhibited cognitive impairments, which were more pronounced in those that underwent surgery. This was accompanied by significant hippocampal neuronal loss, upregulated cleaved caspase-3 expression, and elevated IL-1\u03b2 and TNF-\u03b1 levels. Furthermore, diabetic mice that underwent surgery displayed increased expression of microglial activation markers (Iba-1 and CD68) and evidence of cGAS-STING pathway activation in the hippocampus. Immunofluorescence co-localization experiments further suggested a predominant association of this pathway with the microglial marker Iba-1.Conclusion:These findings suggest that surgery-associated overactivation of the microglial cGAS-STING pathway in the hippocampus may exacerbate neuroinflammation and neuronal injury, thereby contributing to cognitive decline in diabetic mice.<\/jats:p>","DOI":"10.31083\/fbl49331","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":2,"title":["The Role of Hippocampal Microglial cGAS-STING Signaling Pathway in Postoperative Cognitive Dysfunction in Diabetic Mice"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8341-6728","authenticated-orcid":true,"given":"Jiaqi","family":"Ning","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9993-8843","authenticated-orcid":true,"given":"Mengjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5640-5212","authenticated-orcid":true,"given":"Jiaxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4435-3936","authenticated-orcid":true,"given":"Guanzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8923-5737","authenticated-orcid":true,"given":"Siyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1444-7216","authenticated-orcid":true,"given":"Ruyu","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3803-6804","authenticated-orcid":true,"given":"Yuxuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7507-0914","authenticated-orcid":true,"given":"Zhihao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-3422","authenticated-orcid":true,"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Beijing Pinggu District Hospital of Traditional Chinese Medicine, 101200 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-8452","authenticated-orcid":true,"given":"Lingling","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7930-5736","authenticated-orcid":true,"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Lin X, Luo Y, Zhu Q. 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