2017 Fiscal Year Final Research Report
Study on a microglial phenotypic switch with a focus on proteolytic response
| Project/Area Number |
15H05015
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
武 洲 九州大学, 歯学研究院, 准教授 (10420598)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Keywords | ミクログリア / カテプシン / プロテアーゼ反応 / 分子スイッチ |
|---|
| Outline of Final Research Achievements |
The mean mRNA levels of both M1 and M2 markers in microglia acutely isolated from the hippocampus of wild-type mice were gradually and significantly increased after brain injury. In contrast, the mean mRNA levels of M1 markers in microglia acutely isolated from the hippocampus of cathepsin B-deficient mice showed no significant change after brain injury. The mean mRNA levels of the M2 markers increased rather rapidly to reach a peak after brain injury and then returned to the control level. Furthermore, cathepsin E-dependent proteasomal system is involved in an early activation of NF-kB in microglia after brain injury. Autophagy caused a delayed but long-lasting activation of NF-kB through cathepsin B-mediated autophagy machinery in microglia. Therefore, a proteolytic relay through modulator actions of cathepsins E and B could work as a phenotypic switch in microglia along the M1-M2 phenotypic continuum through the dynamics of NF-kB activity.
|
| Free Research Field |
神経薬理学
|
