Molecular mechanisms of transport function at the BBB in epilepsy for normalizing cerebral PGE2 level
Project/Area Number |
16K08365
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | University of Toyama |
Principal Investigator |
Akanuma Shin-ichi 富山大学, 大学院医学薬学研究部(薬学), 助教 (30467089)
|
Co-Investigator(Kenkyū-buntansha) |
細谷 健一 富山大学, 大学院医学薬学研究部(薬学), 教授 (70301033)
|
Research Collaborator |
KUBO Yoshiyuki
TACHIKAWA Masanori
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 血液脳関門 / プロスタグランジン / PGE2 / 有機アニオン輸送担体 / てんかん / L-グルタミン酸 / BBB / 脳毛細血管 / グルタミン酸 |
Outline of Final Research Achievements |
This study aimed to elucidate the mechanism about the attenuation of prostaglandin (PG) E2 efflux transport across the blood-brain barrier (BBB) by L-glutamate, which level is increased in epilepsy. In this study, it is suggested that both PGE2 and PGD2 are eliminated from the brain via organic anion transporter 3 (OAT3) and multidrug resistance-associated protein 4 (MRP4) at the BBB. To examine the detail of the functional alteration of OAT3 and MRP4 at the BBB, an ex vivo transport analysis using isolated rat brain capillaries has been established. Using this analytical method, we demonstrated the attenuation of transport function via OAT3 and MRP4 at the BBB via the activation of NMDA-type L-glutamate receptors. This study could help us to consider the therapeutic strategy to treat the neuroexcitatory diseases, such as epilepsy.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果について、興奮性神経伝達が病態の発現・進行に関与するてんかんなどの中枢神経系疾患に対し、脳内環境正常化を目的とした治療法開発に繋がると期待される。本研究を通じ、NMDA受容体とプロテインキナーゼCがBBBを介したPG排出輸送を調節していることが見出された。そのため、これら疾患時に共に脳内濃度が上昇するPGについて、濃度を正常化する上で、BBBに発現するこれら標的を用いてPGE2排出を促進・正常化することが方策の一つとして提案される。
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Report
(4 results)
Research Products
(23 results)