| Project/Area Number |
16K16456
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Rehabilitation science/Welfare engineering
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
Itoh Hideaki 産業医科大学, 医学部, 助教 (30609201)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | シロスタゾール / 抗血小板薬 / 脳卒中後うつ / 遷延性気分障害 / ノルエピネフリントランスポーター / セロトニントランスポーター / アパシー / 抗うつ作用 / 行動実験 / 脳梗塞後遷延性気分障害 / モノアミントランスポーター / リハビリ進行 |
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| Outline of Final Research Achievements |
Introduction: The antidepressive effects of cilostazol on post-stroke depression have been reported, but the exact mechanism of this action is unknown.The aim of this study was to investigate the direct effects of cilostazol on NET and SERT function.Methods: SK-N-SH and SERT-transfected COS-7 cells were incubated with [3H]norepinephrine (NE) or [3H]serotonin (5-HT) in the presence or absence of cilostazol to assess the monoamine uptake.Results: Cilostazol decreased the [3H]NE uptake by SK-N-SH cells and the [3H]5-HT uptake by SERT-transfected COS-7 cells in a concentration-dependent manner.Conclusions: The blood concentration of cilostazol in treating patients with cerebrovascular disease has been reported to be 13.8 M after a single oral dose of 100 mg. These results indicate that cilostazol inhibit NET and SERT function at clinically relevant concentration, which is likely to show the antidepressant effect on post-stroke depression.
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| Academic Significance and Societal Importance of the Research Achievements |
脳卒中後の遷延性気分障害はリハビリテーション実施の大きな阻害要因になる。今回、培養細胞において抗血小板薬であるシロスタゾールが抗うつ薬と類似したやや弱い作用を持つことが示唆されたことは，シロスタゾールがアパシーやうつ症状などの遷延性気分障害の改善に寄与する可能性が示唆され，今後脳梗塞後の再発予防として投与される抗血小板薬の選択に影響を及ぼす可能性が考えられる。
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