{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:09:10Z","timestamp":1793376550840,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp; Disease"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder, with neuroinflammation playing an important role in its progression to become a major research focus. The role of\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      (\n                      <jats:italic>Pg<\/jats:italic>\n                      ) and its outer membrane vesicles (\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs) in AD development is uncertain, particularly regarding their effects on neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The cognition of mice injected with\n                      <jats:italic>Pg<\/jats:italic>\n                      ,\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs, or PBS via the tail vein was assessed by the Morris water maze test. Pathological changes in the mouse brain were analyzed via immunohistochemistry, immunofluorescence and hematoxylin\u2012eosin (H&amp;E) staining, and the ultrastructure of the hippocampus was observed via transmission electron microscopy (TEM). Plasma levels of inflammatory factors were assessed by enzyme\u2010linked immunosorbent assay (ELISA). Protein levels of brain inflammatory factor, occludin, and NLRP3 inflammasome\u2010related proteins were assessed by western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Memory impairment; notable neuroinflammation, including astrocyte and microglial activation; and elevated protein levels of IL\u20101\u03b2, TNF\u2010\u03b1, and IL\u20106 in the hippocampus were detected in the\n                      <jats:italic>Pg<\/jats:italic>\n                      and\n                      <jats:italic>Pg<\/jats:italic>\n                      OMV groups. However,\n                      <jats:italic>Pg<\/jats:italic>\n                      induced weight loss and systemic inflammation, such as splenomegaly and increased IL\u20101\u03b2 and TNF\u2010\u03b1 levels in plasma, whereas\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs had minimal impact. In addition,\n                      <jats:italic>Pg<\/jats:italic>\n                      induced more pronounced activation of the NLRP3 inflammasome compared to\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs. In contrast, only the\n                      <jats:italic>Pg<\/jats:italic>\n                      OMV group exhibited blood\u2212brain barrier (BBB) disruption characterized by reduced integrity of tight junctions and lower levels of occludin protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pg<\/jats:italic>\n                      is associated with a significant immune response and systemic inflammation, which in turn exacerbates neuroinflammation via activating NLRP3 inflammasome. However,\n                      <jats:italic>Pg<\/jats:italic>\n                      OMVs might elude the systemic immune response and disrupt tight junctions, thereby entering the brain and directly triggering neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70135","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:59:37Z","timestamp":1739264377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["<i>Porphyromonas gingivalis<\/i>\n                    and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms"],"prefix":"10.1002","volume":"13","author":[{"given":"Yu","family":"Qiu","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University Chongqing China"},{"name":"Department of Conservative Dentistry and Endodontics Shanghai Stomatological Hospital &amp; School of Stomatology Fudan University Shanghai China"},{"name":"Center for Neuroscience Research Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Research Chongqing Medical University Chongqing China"},{"name":"Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8715-4576","authenticated-orcid":false,"given":"Guiqiong","family":"He","sequence":"additional","affiliation":[{"name":"Center for Neuroscience Research Chongqing Medical University Chongqing 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