{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:43:23Z","timestamp":1792226603120,"version":"4.4.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alzheimer\u2019s Disease (AD) is a common neurodegenerative disease among the elderly population. It has been posited that the onset and progression of AD are influenced by a combination of various factors. Occlusal support loss due to tooth loss has been reported to be a risk factor triggering cognitive dysfunction. This study aimed to investigate the relationship between tooth loss and cognitive dysfunction and illustrate the role of pyroptosis in advancing Alzheimer\u2019s disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male 5-month-old senescence-accelerated mouse strain P8 (SAMP8) mice were divided into two groups (n = 6): the S (sham-operated) and TL (tooth loss) groups. We assessed spatial memory ability using the Y-maze and Novel Object Recognition (NOR) tests. In addition, we performed pathological and molecular biological assessments of the hippocampus to evaluate pyroptosis-related indicators and changes in cGAS\/STING. We further verified the correlation between the two\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The pathological section staining revealed an upregulation of GSDMD, a target protein of pyroptosis, and abnormal activation of the cGAS\/STING pathway, particularly in microglia, after tooth loss.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , we demonstrated that the BV2 microglia knockdown STING group improved the inflammatory cascade response and down-regulated the pyroptotic features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These data suggest that the occlusal support loss due to tooth loss induces pyroptosis-related protein deposition, which may be intimately associated with the cGAS\/STING signaling pathway. This provides new insights into the treatment and prevention of oral health and cognitive behavioural disorders in the elderly population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2025.1628520","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:27:21Z","timestamp":1755840441000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Tooth loss impairs cognitive function in SAMP8 mice by aggravating pyroptosis of microglia via the cGAS\/STING pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Xu","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunping","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangqi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixiang","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/j.joen.2024.06.012","article-title":"Tooth loss is a risk factor for cardiovascular disease mortality: a systematic review with meta-analyses","volume":"50","author":"Aminoshariae","year":"2024","journal-title":"J. Endodont."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1017\/S135561771700100X","article-title":"Alzheimer's disease: past, present, and future","volume":"23","author":"Bondi","year":"2017","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1125759","DOI":"10.3389\/fimmu.2023.1125759","article-title":"Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING\/IRE1\u03b1 pathway after traumatic brain injury in mice","volume":"14","author":"Cao","year":"2023","journal-title":"Front. 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Psychiatry"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.amjmed.2023.04.008","article-title":"Association of tooth loss and diet quality with acceleration of aging: evidence from NHANES","volume":"136","author":"Xu","year":"2023","journal-title":"Am. J. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"111195","DOI":"10.1016\/j.cellsig.2024.111195","article-title":"The cGAS\/STING signaling pathway is involved in sevoflurane induced neuronal necroptosis via regulating microglia M1 polarization","volume":"119","author":"Zhang","year":"2024","journal-title":"Cell. Signal."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/jnr.24385","article-title":"Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro","volume":"97","author":"Zhang","year":"2019","journal-title":"J. Neurosci. Res."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1628520\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:27:21Z","timestamp":1755840441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1628520\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":41,"alternative-id":["10.3389\/fnagi.2025.1628520"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2025.1628520","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]},"article-number":"1628520"}}