| Project/Area Number |
13670627
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
KATO Hiroyuki Tohoku University, Graduate School of Medicine, Associate professor, 大学院・医学系研究科, 助教授 (60224531)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ITOYAMA Yasuto Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30136428)
TAKAHASHI Akira Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40301048)
ARAKI Tsutomu Tohoku University, Graduate School of Pharmaceutical Science, Associate professor, 大学院・薬学研究科, 助教授 (80323038)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Celebral ischemia / Celecral infarction / Neuronal death / Parkinson's disease / MPTP / Dopamine / Microglia / Astroglia / ミクロダリア |
|---|
| Research Abstract |
The purpose of this study was to clarify the role of glial cells in the development of ischemia-induced and MPTP-induced neuronal deaths. (1) Cerebral ischemia (10 min) was induced by the 2-vessel occlusion method in rats, which were sacrificed after 1 day, 2 days, and 7 days for double label immunohistochemistry. Expression of cell cycle proteins occurred prior to CAI neuronal death, and played a role in microglial proliferation. Proliferating cell nuclear antigen (PCNA) was expressed in 83% of microglial cells in CAI after 2 days. The number of microglial cells increased by 7.6-fold after 7 days CAI neurons were depleted. Cell cycle proteins, cyclin D1 and cdk4, were induced in microglia in a similar fashion. PCNA was expressed only in 6% of astrocytes in CAI after 7 days, when astroglial proliferation was only 1.8-fold. We observed no cell cycle protein expression in neurons. (2) MPTP (20 mg/kg) was injected i.p. 4 times 2 hr apart to mice. The content of dopamine in striatum was reduced to 16% of control after 1 day, and was remained as low as 22% after 14 days. ONO-2506, an astroglial function modulating agent, administered immediately, 6 hr, 24 hrs, 48 hrs, and 72 hrs after MPTP injection prevented the dopamine depletion, and led to better performance in behavioral tests. Astrocytes in striatum were activated markedly after 7 days, and ONO-2506 treatment resulted in earlier activation of asrtrocytes. The findings suggest that astrocytes may be a target for neuroprotection in MPTP induced neuronal death, and possibly in Parkinson's disease.
|
