2021 Fiscal Year Final Research Report
Effect of Nox4, a major NADPH-dependent reactive oxygen species-producing enzyme, on cerebral demyelination and cognitive impairment due to chronic cerebral hypoperfusion
Project/Area Number |
19K09530
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
|
Research Institution | Kyushu University |
Principal Investigator |
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Keywords | 慢性脳低灌流による脳脱髄 / 薬剤誘発脳脱髄 / Nox4 / 脳血管性認知症 / ミクログリア / マクロファージ / アストロサイト / オリゴデンドロサイト前駆細胞 |
Outline of Final Research Achievements |
Genetic deletion of Nox4 enhances demyelination, suppresses angiogenesis and infiltration of astrocyte and microglia, reduces differentiation and proliferation of oligodendrocyte precursor cells (OPC), and impairs spatial cognition following chronic cerebral hypoperfusion. Thus, Nox4 could repress demyelination by promoting differentiation and proliferation of OPC through trophic factors released by infiltrating astrocytes and microglia. However, in the cuprizone (CPZ)-induced demyelination model, genetic deletion of Nox4 enhances remyelination through increasing phagocyte capacity of microglia and macrophage. Therefore, we have found contradicting effects of Nox4 in 2 demyelination models. It will be a near future study to investigate the discrepancy of effect of Nox4 between demyelination by chronic cerebral hypoperfusion and CPZ.
|
Free Research Field |
急性また慢性の脳血管障害また認知症の病態解明
|
Academic Significance and Societal Importance of the Research Achievements |
慢性脳低灌流による脳白質障害は認知症の発症や病態増悪の要因となるが、脳白質障害の発症や進展を抑制する有効な治療法は未だ確立していない。今回、慢性脳低灌流下ではNox4は脳保護的に作用して脱髄の改善を示したが、一方で薬剤誘発性脱髄ではNox4は脱髄遷延をもたらすことを見出した。Nox4による脳白質障害の発症・進展を抑制する機序をさらに詳細に検討し、今後の認知症治療の開発につなげたい。
|