| Project/Area Number |
16590071
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Kyoto Pharmaceutical University |
|---|
Principal Investigator |
KITAMURA Yoshihisa Kyoto Pharmaceutical University, Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60195295)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Microglia / Mouse embryonic stem cells / Neural precursors / Dopaminergic neurons / Nigro-striatal pathway / Parkinson's disease / Subthalamic nucleus / Brain ischemia / アストロサイト / アミロイドβ / アルツハイマー病 |
|---|
| Research Abstract |
Middle cerebral artery occlusion (MCAo) and reperfusion caused behavioral dysfunction with massive neuronal loss in the rat cerebral cortex and striatum. When exogenous microglia were transplanted into the i.c.v. during MCA occlusion, focal ischemia-induced behavioral dysfunction was significantly inhibited. At that time, many microglia migrated into the ischemic lesion, and microglia-derived neuron-like cells were barely detectable. These results suggest that exogenous microglia protect against focal ischemia-induced neurodegeneration and improve behavioral dysfunction.
To investigate a transplantation strategy for Parkinson's disease, we assessed whether double-transplants in the striatum (ST) and substantia nigra (SN), or ST and subthalamic nucleus (STN) induce functional recovery in 6-hydroxydopamine-lesioned rats. Methamphetamine-induced rotation was significantly reduced by transplantation of mouse ES cell-derived neurons into the ST, but not the STN or SN alone. Double-transplantation was also effective at recovering rotational behavior. Although immunoreactivity for tyrosine hydroxylase (TH) was almost completely lost in the ipsilateral striatum in hemiparkinsonian rats, TH immunoreactivity was detected in transplanted cells and sprouting fibers in the ST, STN and SN. These results suggest that both the involvement of ST and as a place of transplantation and the number of ES cell-derived neurons are essential factors for efficacy on hemiparkinsonian behaviors.
|
