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Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1ß Production in Leptomeningeal Cells.
Huang, Wanyi; Zeng, Fan; Gu, Yebo; Jiang, Muzhou; Zhang, Xinwen; Yan, Xu; Kadowaki, Tomoko; Mizutani, Shinsuke; Kashiwazaki, Haruhiko; Ni, Junjun; Wu, Zhou.
Afiliación
  • Huang W; Department of Aging Science and Pharmacology>, Faculty of Dental Science, Kyushu University, Fukuoka Japan.
  • Zeng F; Department of Aging Science and Pharmacology>, Faculty of Dental Science, Kyushu University, Fukuoka Japan.
  • Gu Y; Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth and Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
  • Jiang M; Department of Aging Science and Pharmacology>, Faculty of Dental Science, Kyushu University, Fukuoka Japan.
  • Zhang X; Center of Implant Dentistry, School of Stomatology, China Medical University, Shenyang, China.
  • Yan X; The VIP Department, School of Stomatology, China Medical University, Shenyang, China.
  • Kadowaki T; Division of Frontier Life Science, Department of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
  • Mizutani S; Section of Geriatric Dentistry and Perioperative Medicine in Dentistry, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
  • Kashiwazaki H; OBT Research Center, Faculty of Dental Sciences, Kyushu University, Fukuoka, Japan.
  • Ni J; Section of Geriatric Dentistry and Perioperative Medicine in Dentistry, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
  • Wu Z; Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Haidian District, Beijing, China.
J Alzheimers Dis ; 83(2): 665-681, 2021.
Article en En | MEDLINE | ID: mdl-34334391
BACKGROUND: Studies have reported that synaptic failure occurs before the Alzheimer's 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-1ß 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-1ß 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-1ß 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-1ß 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-1ß production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Bacteroidaceae / Porphyromonas gingivalis / Proteína con Dominio Pirina 3 de la Familia NLR / Meninges Límite: Animals / Female / Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Bacteroidaceae / Porphyromonas gingivalis / Proteína con Dominio Pirina 3 de la Familia NLR / Meninges Límite: Animals / Female / Humans Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos