Mechanisms of sepsis-associated brain dysfunction in the senescence-accelerated mouse
| Project/Area Number |
18K16527
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Hoshino Koji 北海道大学, 大学病院, 助教 (40802434)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 敗血症関連脳障害 / シナプス可塑性 / 神経炎症 / 敗血症 / 認知機能障害 |
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| Outline of Final Research Achievements |
Aging and pre-existing cognitive impairment are considered to be independent risk factors for sepsis-associated encephalopathy. We aimed to investigate the manner in which aging and pre-existing cognitive dysfunction modified neuroinflammation and synaptic function using senescence-accelerated mice. We demonstrated that sepsis increased IL-1β levels in the hippocampus concomitant with microglial activation and decreased basal synaptic transmission, especially in senescence mice. Meanwhile, sepsis did not decrease the basal synaptic transmission, but impaired the synaptic plasticity in the non-senescence mice. These changes were reversed by the administration of the IL-1 receptor antagonist, meaning that IL-1 receptor-associated mechanisms were involved with these changes of the synaptic function.
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| Academic Significance and Societal Importance of the Research Achievements |
認知症合併高齢者における、敗血症罹患後の認知機能障害は予後に影響を及ぼすだけではなく、患者の生活の質を著しく損なうため社会的に大きな問題となる。本研究で示したシナプス可塑性の変化は、認知機能を反映する細胞学的モデルと考えられており、IL-1受容体の拮抗により認知機能改善の可能性があることを示した。敗血症関連脳障害を予防する治療薬は未だ存在しないが、本研究の結果からIL-1受容体を標的とした治療薬の開発が望まれる。
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Report
(4 results)
Research Products
(4 results)
