| Project/Area Number |
17K10277
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | University of Miyazaki |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
西森 利数 宮崎大学, 医学部, 特別教授 (20112211)
蛯原 功介 宮崎大学, 医学部, 助教 (20510720)
|
|---|
| Project Period (FY) |
2017-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | パーキンソン病 / L-DOPA / アストロサイト / オプトジェネティクス / 6-hydroxydopamine / 不随意運動 / オプトジェネティックス / レボドパ / 光遺伝学 |
|---|
| Outline of Final Research Achievements |
Unilateral 6-hydroxydopamine (6-OHDA) lesions were produced in the nigrostriatal pathway in rats. Despite the marked loss of the striatal immunoreactivity of tyrosine hydroxylase on the lesion side, striatal serotonin (5-HT) immunoreactivity was not affected. A treatment with L-DOPA in conjunction with benserazide for 15 days induced abnormal involuntary movements (AIMs) including locomotive (rotational response), axial, forelimb, and orolingual movements in lesioned rats. The L-DOPA-induced locomotive and axial, but not forelimb and orolingual, AIMs were significantly increased and prolonged by the pre-administration of YKS. We next examined the effects of YKS on the production of DA from L-DOPA in 5-HT synthetic RIN 14B cells. RIN 14B cells produced DA and its metabolite 3-methoxytyramine (3-MT) following L-DOPA treatment. YKS significantly augmented DA production and inhibited its metabolism to 3-MT, similar to the catechol-O-methyltransferase (COMT) inhibitor entacapone.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により，L-DOPA慢性投与後に出現する不随意運動発現機序の解明，治療法開発の一助になり得るものと考える。更には，不随意運動と共通の生物学的基盤が介在している可能性の高いL-DOPA誘発性の精神症状の病態解明にも貢献しうると考える。
本研究の成果により，現在認知症をはじめとする高齢患者の不眠や神経症症状に頻用されている抑肝散が，抗パーキンソン病薬と共通した作用（COMT阻害作用）有していることが明らかとなった。
|
