Project/Area Number |
26293438
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Periodontology
|
Research Institution | National Center for Geriatrics and Gerontology |
Principal Investigator |
MATSUSHITA Kenji 国立研究開発法人国立長寿医療研究センター, 口腔疾患研究部, 部長 (90253898)
|
Co-Investigator(Kenkyū-buntansha) |
多田 浩之 東北大学, 歯学研究科, 講師 (70431632)
萩原 真 国立研究開発法人国立長寿医療研究センター, 口腔疾患研究部, 流動研究員 (30546099)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
|
Keywords | 認知症 / 歯周病 / 歯周病原細菌 / 神経炎症 / アミロイドβ / ミクログリア / 血液脳関門 / Porhyromonas gingivalis / アルツハイマー病 / Porphyromonas gingivalis / 酸化ストレス / 慢性炎症 / 生活習慣病 / 因果関係 / 歯周病関連細菌 |
Outline of Final Research Achievements |
We investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P.gingivalis-inoculated mice. P. gingivalis LPS induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P.gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.
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