{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:39:19Z","timestamp":1779907159564,"version":"3.53.1"},"reference-count":51,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,9,14]]},"abstract":"<jats:p>Background: Studies have reported that synaptic failure occurs before the Alzheimer\u2019s disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1\u03b2 in response to systemic inflammation. Objective: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. Methods: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1\u03b2 production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). Results: Systemic P. gingivalis infection increased the expression of IL-1\u03b2 in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1\u03b2 secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. Conclusion: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB\/NLRP3 inflammasome-mediated IL-1\u03b2 production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.<\/jats:p>","DOI":"10.3233\/jad-210031","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T13:14:13Z","timestamp":1627391653000},"page":"665-681","source":"Crossref","is-referenced-by-count":11,"title":["Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1\u03b2 Production in Leptomeningeal Cells"],"prefix":"10.1177","volume":"83","author":[{"given":"Wanyi","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Aging Science and Pharmacology>, Faculty of Dental Science, Kyushu University, Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Aging Science and Pharmacology>, Faculty of Dental Science, Kyushu University, Fukuoka 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