| Project/Area Number |
25460090
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Pharmacology in pharmacy
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
Shioda Norifumi 東北大学, 薬学研究科(研究院), 特任准教授 (00374950)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUKUNAGA Kohji 東北大学, 大学院薬学研究科, 教授 (90136721)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 精神疾患 / ドパミン D2 受容体 / シグナル伝達 / 細胞内シグナル伝達 / PDGF 受容体 / Rabex-5 / 行動制御回路 / ドパミンD2L受容体 / PDGF 受容体-β / スプライスバリアント |
|---|
| Outline of Final Research Achievements |
Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. We found that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits ERK activation and dendritic spine formation through Rabex-5/PDGFRβ-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early endosome formation. In addition, dendritic spine density in striatopallidal MSNs significantly increased following treatment of striatal slices from wild-type mice with quinpirole, a D2R agonist, but those changes were lacking D2LR knockout mice. Moreover, intracellular D2LR signaling mediated effects of a typical antipsychotic drug, haloperidol, in inducing catalepsy behavior. Taken together, intracellular D2LR signaling through Rabex-5/PDGFRβ is critical for ERK activation and neuronal activity in striatopallidal MSNs of mice.
|
