| Project/Area Number |
15K09324
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
安部 貴人 大阪市立大学, 大学院医学研究科, 准教授 (30365233)
中原 仁 慶應義塾大学, 医学部(信濃町), 助教 (60537950)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | ケトン体 / βヒドロキシ酪酸 / アストログリア / ミクログリア / 脳虚血モデル / フマル酸ジメチル / アストロサイト / オリゴデンドロサイト / 髄鞘イメージング / 一酸化窒素 / ＴＬＲ４ / 脳虚血 |
|---|
| Outline of Final Research Achievements |
Astroglia produce and release ketone bodies, especially beta-hydroxybutyrate (BHB) by ischemic insult. BHB plays a neuroprotective role in various neurological disorders. Dimethyl fumarate (DMD), used as a disease modifying drug for multiple sclerosis patients, has been found to be a ligand of HCAR2. BHB also acts as a ligand for HCAR2. We have hypothesized that astroglia-derived BHB reduces infarct volume and improves neurological function after a transient middle cerebral artery occlusion (tMCAO). tMCAO was performed in male C57BL/6 mice and Nrf2-/- mice. Infarct volume and neurological function assessed by hanging wire test was significantly improved by DMF treatment both in C57BL/6 mice and in Nrf2-/- mice, suggestive of a Nrf2-independent mechanism. In cultured central nervous system cells, DMF upregulated the expression HO-1 which is most common downstream gene of Keap1 / Nrf2 system. Importantly, however, both BHB and DMF may play neuroprotective roles through HCAR2.
|
