| Project/Area Number |
17591138
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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 | The University of Tokyo |
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Principal Investigator |
KAMEI Yoshimasa The University of Tokyo, The Univetsity of Tokyo Hospital, Assistant Professor (00251265)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Apoptosis / Oligodendrocyte / Periventricular leukomalacia / DNA microarray / 脳質周囲白質軟化証 / Bax / 神経細胞 / 内分泌撹乱物質 / エストロゲン / ビスフェノールA / グルタミン酸 / 小脳顆粒細胞 |
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| Research Abstract |
Glutamate-induced neuronal cell death has been implicated in the pathogenesis of neonatal hypoxic-ischemic brain injury and other neurodegenerative diseases. To investigate the possibility of a new neuroprotection strategy targeting Bax translocation in glutamate-induced neuronal cell death, cerebellar granule neurons (CGNs) were exposed to glutamate with or without BIP, a novel membrane-permeable peptide which can bind Bax in the cytosol and inhibit its translocation to the mitochondria. Pretreatment of CGNs with BIP elicited a dose-dependent reduction of glutamate-induced neuronal cell death as measured by the MTT assay. BIP significantly suppressed both the number of TUNEL-positive cells and the increase in caspase 3 and caspase 9 activities induced by glutamate. In addition, immunoblots after subcellular fractionation revealed that BIP prevented the glutamate-induced Bax translocation to the mitochondria and the release of cytochrome c from the mitochondria. These results suggest that agents capable of inhibiting Bax activity such as BIP might lead to new drugs for glutamate-related diseases in the future.
Oligodendrocytes (Ols) have been implicated to be the main player in the development of periventricular leukomalacia in the perinatal period. Recently, hypothermia therapy for the neonates with hypoxic-ischemic brain injurues has been reported to be effective for the protection of the neurological disabilities. We investigated the mechanism of the hypothermia on the OL function using primary culture of Ols. We found proliferation of Ols is at maximum at lower temperature and DNA microarray analysis proved that many genes are involved in this process. We will further analyze the mechanism of the proliferation of Ols.
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