2021 Fiscal Year Final Research Report
Elucidation and treatment development of the pathophysiology of glutamate-D-serine system in the white matter of schizophrenia
| Project/Area Number |
18K07548
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52030:Psychiatry-related
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Keywords | D-セリン / 白質 / 灰白質 / 大脳皮質 / ニューロン / グリア / 免疫組織化学 / in vivoダイアリシス |
|---|
| Outline of Final Research Achievements |
In the white matter of the mouse prefrontal cortex, D-serine concentrations in tissue and extracellular fluid were nearly equal to those in gray matter. D-Serine in the white and gray matter of the prefrontal cortex was significantly reduced in mice treated with cuprizone, which primarily destroys oligodendroglia (ODG), and D-serine was markedly reduced in the gray matter of the prefrontal cortex injected locally with quinolinic acid, which selectively degenerates neuronal cell bodies. Immunohistochemical analysis suggested the presence of D-serine in the white matter ODG. These results suggest that D-serine may localize to the intrafascicular ODG in the white matter and to neurons and perineuronal ODG in the gray matter, drawing attention to the relationship between dysfunctions of D-serine and ODG , which have been presumed to be involved in the pathophysiology of schizophrenia.
|
| Free Research Field |
精神神経科学
|
| Academic Significance and Societal Importance of the Research Achievements |
D-セリンは、NMDA受容体の内在性のコアゴニストであり、同受容体の低活性が推測される統合失調症における異常が注目されている。本研究では、D-セリンが、グリア優位の白質でニューロン優位の灰白質と同程度の組織中・細胞外液中の濃度を維持し、オリゴデンドログリア（ODG）に含まれることを見出した。また、灰白質ではニューロンに多く局在するだけでなく、傍神経ODGにも存在する可能性が示唆された。これら新知見は、D-セリンシグナルの分子細胞機構とその病態の解明の手がかりになるとともに、D-セリンを調節する統合失調症の難治性症状に対する新規治療法開発に繋がる、重要な学術的・社会的意義をもつと考えられる。
|
