Cerebrovascular unit disruption in bipolar disorder model: Involvement of redox signaling mechanism
Project/Area Number |
15K18865
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Biological pharmacy
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Research Institution | Kumamoto University |
Principal Investigator |
Kurauchi Yuki 熊本大学, 大学院生命科学研究部(薬), 助教 (70631638)
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | Na+, K+-ATPase / 脳血管障害 / 双極性障害 / 精神疾患 / グルタミン酸 / 血管内皮細胞 / レドックスシグナル / 8-nitro-cGMP / 脳血流 / グリア細胞 |
Outline of Final Research Achievements |
In this study, I established novel in vitro model to evaluate the degeneration mechanism of cerebrovascular unit. I prepared brain slices containing prefrontal cortex region from neonatal rats, and treated ouabain, an inhibitor of Na+, K+-ATPase. Treatment with ouabain induced degeneration of cerebrovascular endothelial cells, but not pericytes. For the protective mechanism of cerebrovascular endothelial cells and pericytes, I found that activation of PI-3kinase/Akt signaling pathway plays an endogenous protective mechanism against Na+, K+-ATPase dysfunction. Furthermore, I found that treatment with ouabain induces neuronal cell death and activates glial cells. These results suggest that activation of microglia and astrocytes causes degeneration of cerebrovascular endothelial cells and neurons in the prefrontal cortex region. These abnormalities may contribute to the pathophysiology of several psychiatric disorders including bipolar disorder.
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Report
(3 results)
Research Products
(59 results)
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[Journal Article] Inhibition of Leukotriene B4 Action Mitigates Intracerebral Hemorrhage-Associated Pathological Events in Mice2017
Author(s)
Hijioka, M., Anan, J., Ishibashi, H., Kurauchi, Y., Hisatsune, A., Seki, T., Koga, T., Yokomizo, T., Shimizu, T.,Katsuki, H.
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Journal Title
J Pharmacol Exp Ther
Volume: 360
Issue: 3
Pages: 399-408
DOI
Related Report
Peer Reviewed
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[Journal Article] Effects of cyclodextrins on GM1-gangliosides in fibroblasts from GM1-gangliosidosis patients.2015
Author(s)
Maeda Y, Motoyama K, Higashi T, Horikoshi Y, Takeo T, Nakagata N, Kurauchi Y, Katsuki H, Ishitsuka Y, Kondo Y, Irie T, Furuya H, Era T, Arima H.
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Journal Title
J Pharm Pharmacol.
Volume: 67
Issue: 8
Pages: 1133-1142
DOI
Related Report
Peer Reviewed / Open Access
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