Regulation of blood-brain barrier by neuro-vascular units and the involvement in schizophrenia
| Project/Area Number |
17K17979
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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 |
Human pathology
Nerve anatomy/Neuropathology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Research Collaborator |
Chiba Hideki
Sugimoto Kotaro
Tomikawa Naoki
Takahashi hitoshi
Kakita Akiyoshi
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 神経血管ユニット / 血液脳関門 / 統合失調症 / クローディン / PKA / セロトニン / モノアミン / 血管内皮 / 病理学 / タイト結合 |
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| Outline of Final Research Achievements |
We found that the serotonin receptor 5-HT1A is strongly expressed in microvascular endothelial cells and pericyte. Using a novel co-culture system of these cells, we showed that serotonin/5-HT1A signaling regulates endothelial claudin-5 (CLDN5) expression. On the other hand, protein kinase A (PKA) was activated in the microvascular and perivascular regions of the schizophrenic prefrontal cortex (PFC), and the pPKA-positive microvascular endothelial cells occasionally showed focal loss of CLDN5. These alterations were brain-region selective, and not observed in normal brain. Thus, serotonin/5-HT1A/cAMP/PKA signaling contributes to
regulate endothelial CLDN5 expression and blood-brain barrier in brain-site specific manners.
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症ではセロトニン仮説等が提唱されているが、その病態は不明である。代表者は統合失調症前頭前野の微小血管選択的にprotein kinase A (PKA)が活性化し、その部位に一致して血液脳関門構成分子であるclaudin-5 (CLDN5)が部分消失していることを発見した。また5-HTが5-HT1A受容体を介して血液脳関門を制御する新規機構を発見した。セロトニン/5-HT1A/cAMP/PKAシグナルの破綻が統合失調症の病態に関与する可能性が示された。
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Report
(3 results)
Research Products
(3 results)
