2018 Fiscal Year Final Research Report
The Effects of Astrocyte and Oligodendrocyte Lineage Cell Interaction on White Matter Injury under Chronic Cerebral Hypoperfusion
Project/Area Number |
16K07067
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | Juntendo University |
Principal Investigator |
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Keywords | cell-cell interaction / oligodendrogenesis |
Outline of Final Research Achievements |
We examined the effects of the interaction between astrocyte and oligodendrocyte lineage cells on myelination regarding the mechanism of impairment. White matter injury progressed in the BCAS model as myelin decreased. The numbers of OPCs and astrocytes increased after the operation, whereas that of OLGs decreased at day 28. BDNF continuously decreased until day 28. Differentiation was disrupted under the stressed conditions in the cell culture, but improved after administration of astrocyte-conditioned medium containing BDNF. Astrocytes with BDNF underwent differentiation, but differentiation was impaired under the stressed conditions due to the reduction of BDNF. We examined S100B regarding the mechanism of impairment. S100B is mainly expressed by mature astrocytes. GFAP-positive astrocytes increased in the corpus callosum in the BCAS model, whereas the number of mature astrocytes continued to decrease, resulting in reduced BDNF.
|
Free Research Field |
神経内科学
|
Academic Significance and Societal Importance of the Research Achievements |
オリゴデンドロサイトの再生に関しては多発性硬化症研究の分野では報告があるものの,虚血性白質障害の分野においての報告はいまだ数少ない.我々が考案した本研究は,脳虚血領域の中でも慢性期の病態に焦点を絞ることができ,さらにはいまだ有効な治療方法のない慢性期虚血性白質障害の治療に一石と投じれると考えられる.また、その役割機能を解明することは今日,社会的問題にもなっているアルツハイマー型認知症の克服にも発展的臨床応用が可能になると考える.BDNFを代表とするアストロサイトからの栄養因子強化は,白質保護につながるだけではなく,血管性認知症の治療ターゲットになる可能性が示せた.
|