| Project/Area Number |
20790607
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Hirosaki University |
|---|
Principal Investigator |
ARAI Akira Hirosaki University, 大学院・医学研究科, 客員研究員 (80422062)
|
|---|
| Project Period (FY) |
2008 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
|
|---|
| Keywords | パーキンソン病 / L-DOPA誘発ジスキネジア / 淡蒼球内節 / GABA / GABA_A受容体 |
|---|
| Research Abstract |
We hypothesized that abnormal GABA transmission in the MGP is involved in the occurrence of L-DOPA induced dyskinesia (LID). The results of this study, using in vivo microdialysis, confirmed this hypothesis. L-DOPA challenge increased GABA release in the MGP on the lesioned side in both LID-model and PD-model rats but significantly more so in LID-model rats. To confirm that stimulation of GABA receptors in the MGP induces dyskinesia-like abnormal involuntary movements (AIMs) and inhibition of GABA transmission in the MGP improves L-DOPA-induced AIMs, we performed microinjection of GABAA receptor agonist (muscimol) and antagonist (bicuculline) into the MGP on the lesioned side of 6-OHDA-lesioned PD-model rats. We could show that injection of muscimol induced AIMs same as those induced by L-DOPA. In addition, microinjection of bicuculline significantly alleviated L-DOPA-induced AIMs and L-DOPA-induced AIMs revived after discontinuation of bicuculline microinjection. Thus, we could evidence that activation of GABAA receptors in the MGP of PD-model rats induced dyskinesia-like AIMs and inhibition of GABA signaling in the MGP of PD-model rats improved L-DOPA-induced AIMs.
|
