| Project/Area Number |
17591140
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
TSUNEISHI Syuichi Kobe University Hospital, Associate Professor, 医学部附属病院, 助教授 (10271040)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Naoki Kobe University Hospital, Lecturer, 医学部附属病院, 講師 (20314487)
森沢 猛 神戸大学, 医学部附属病院, 助手 (30379375)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | apoptosis / myelination / protease-activated receptor 1 / proteolipid protein (PLP) / myelin basic protein (MBP) / white matter injury / MRS / ADEM / 低酸素性虚血性脳症 / 新生児 |
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| Research Abstract |
The aim of this study is to exploit a new strategy to prevent and treat neonatal cerebral white matter injury against hypoxic-ischemic insult through regulating apoptosis of glial cells.
We determined that activation of protease-activated receptor-1 (PAR-1), one of potent thrombin receptors, suppresses the differentiation of glial cells and protects them against various injurious insults. Administration of TRAP-14, an agonist of PAR-1, into the glial cell culture prevents the expression of proteolipid protein (PLP) gene induced by retinoic acid in rat glioblastoma cell, C6. A strong inhibitor of PAR-1, E5510 (Eizai) can accelerate the expression of PLP gene in the same laboratory setting. Anti-sense oligo-DNA of PAR-1 covering initiation codon sequence can also reduce the PLP mRNA levels. Activation of PAR-1 has a crucial role in the regulation of differentiation of glial cells.
In clinical cases with white matter disorders detected by MRI scan, we evaluated the status of energy metabolism and gene analysis of myelin-relating genes. In a severe ADEM case, we identified the normal metabolic status using ^3H-MRS at high intensity region on FLAIR scan. In a dysmorphism case carrying white matter dysgenesis on MRI scan, a partial deletion of 18q was found in G-banding and we could confirm the lack of myelin basic protein gene locus using CGH method and MBP FISH. Haploinsufficiency of MBP gene is proved to be a cause of dysgenesis of myelin tissue.
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