| Project/Area Number |
17K11670
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | Daiichi University, College of Pharmaceutical Sciences (2019)
Hiroshima University (2017-2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
兼松 隆 九州大学, 歯学研究院, 教授 (10264053)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 歯周病モデル / PgLPS / ミクログリア / 炎症性サイトカイン / NF-κB / 抗うつ薬 / 歯周病 / 炎症 / 神経細胞 / 中枢機能障害 / 歯性感染 / 免疫 |
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| Outline of Final Research Achievements |
We investigated whether peripheral inflammation caused by periodontal disease spreads to the central nervous system, which causes neuro-inflammation and stress vulnerability, and whether antidepressants suppress them using periodontal disease model mice and cultured cells. As a result, lipopolysaccharide derived from P. gingivaris (PgLPS) caused microglial activation and inflammatory response in the hippocampus. In addition, PgLPS caused neuronal cell death by inducing an inflammatory response by activating the NF-κB pathway via TLR2/4 in microglia. Furthermore, antidepressants suppressed microglia-induced neuronal cell death by inhibiting the NF-κB pathway in microglia. In mice, antidepressants also suppressed hippocampal inflammation and tended to suppress PgLPS-induced depression-like behavior.
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| Academic Significance and Societal Importance of the Research Achievements |
歯周病はP.gingivarisなどの細菌が口腔に感染することで引き起こされる慢性的な局所炎症であるが、この炎症は全身へと波及し、心疾患や糖尿病などの全身疾患のみならず、認知機能障害のリスクファクターであることが明らかとなってきた。本研究は、歯周病への罹患がストレス脆弱性にも関与する可能性とその機序を示し、また既存の抗うつ薬が歯周病による中枢炎症を抑制することを示した。歯周病のリスクを知らしめることで認識を改め、また治療薬の可能性を示したという点で意義があると考える。
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