Regulation od dopamine transpoter activity by protein tyrosine phosphatase
| Project/Area Number |
17K07069
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurophysiology / General neuroscience
|
|---|
| Research Institution | National Institute for Basic Biology |
|---|
Principal Investigator |
Akihiro Fujikawa 基礎生物学研究所, 神経生理学研究室, 特別訪問研究員 (50414016)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | チロシンホスファターゼ / 覚せい剤 / 海馬 / 記憶 / 学習 / 脳神経 / ドーパミン神経 / チロシンリン酸化 / ドーパミントランスポータ / ドーパミントランスポーター / 依存 / 阻害化合物 / 神経科学 / シグナル伝達 |
|---|
| Outline of Final Research Achievements |
This study aimed to identify the signaling pathway of a receptor-type protein tyrosine phosphatase, PTPRZ, in hippocampus-dependent learning and memory, or methamphetamine dependence. We performed behavioral studies on two newly generated knock-in mouse lines: One expresses the catalytically inactive mutant of PTPRZ (Ptprz-CS), while the other expresses constitutively active mutant lacking the negative regulatory D2 (Ptprz-ΔD2). The results suggested that the phosphatase activity of PTPRZ was not essential for the hippocampus-dependent memory, but its absence caused decreases in behavioral responses to methamphetamine. Furthermore, in this study, we revealed that the structural basis for ligand-induced inactivation of PTPRZ and its physiological relevance by comparing the phenotypes of Ptprz-mutant mice.
|
| Academic Significance and Societal Importance of the Research Achievements |
海馬依存の恐怖文脈条件付け学習や覚せい剤依存形成に関わるPTPRZシグナルを解明することで、心的外傷後ストレス障害（PTSD）や薬物依存に関わる分子基盤の理解を進め、その治療に向けた新しい創薬戦略の創出に貢献する意義を有する。
|
Report
(4 results)
Research Products
(5 results)
