Project/Area Number |
25461641
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Embryonic/Neonatal medicine
|
Research Institution | Saitama Medical University |
Principal Investigator |
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | 脳室周囲白質軟化症 / 低酸素虚血性脳症 / マイクログリア / 脳低温療法 / ミエリン塩基性蛋白 / ミクログリア / クロドロネート / リポソーム / 脳低体温療法 / ノルエピネフリン / CREB / IL-1b / オリゴデンドロサイト |
Outline of Final Research Achievements |
We investigate the effectiveness and mechanism of hypothermia for the inhibition of pre-OLs damage in PVL using in vivo and I vitro studies. For in vivo studies, the loss of myelin basic protein (MBP) was inhibited by hypothermia. For in vitro studies, hypothermia inhibited apoptosis of pre-OLs, and despite specific down-regulation of 21.5- and 17-kDa MBP mRNA expression during hypothermia, recovery of the expression after OGD was superior compared with normothermia. OGD caused disarrangement of MBP distribution, decreased levels of phosphorylated 21.5-kDa MBP, and disturbed the capacity to contact with neurons, all of which were restored by hypothermia. U0126 treatment during/after OGD significantly reduced the protective effects of hypothermia on apoptosis and myelination, respectively. These data suggest that phosphorylated exon 2-containing MBP isoforms may play critical roles in myelination via ERK1/2 phosphorylation.
|