2022 Fiscal Year Final Research Report
Pathophysiology and treatment for levodopa-induced dyskinesia in a rat model of Parkinson's disease
Project/Area Number |
20K16570
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52020:Neurology-related
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Research Institution | Hirosaki University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | レボドパ誘発ジスキネジア / パーキンソン病 / シナプス可塑性 / 樹状突起上スパイン / 淡蒼球内節 / 直接路 / アマンタジン / カベルゴリン |
Outline of Final Research Achievements |
I created unilateral Parkinson's disease model rats and treated them with levodopa. Levodopa treatment induced dyskinesia-like abnormal involuntary movements in model rats. Globus pallidus internus was enlarged in the dyskinesia model. Using an electron microscopy, I found that nerve terminals of the direct pathway striatal projection neurons in the globus pallidus internus showed remarkable hypertrophy including massive GABA and that this hypertrophy gradually progressed along with repeated levodopa treatment. The effects of cabergoline and amantadine on dyskinesia were investigated in the same dyskinesia models and I have published two papers. In addition, I found that dyskinesia was mild in an aged model and that enlargement of globus pallidus internus and overexpression of dynorphin in the striatum with dyskinesia were suppressed with aging. I published a paper on these finding. I also wrote a review paper on the pathogenesis of levodopa-induced dyskinesia.
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Free Research Field |
医歯薬学
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Academic Significance and Societal Importance of the Research Achievements |
社会の高齢化に伴いパーキンソン病はパーキンソン・パンデミックと呼ばれるほど患者数が増加してきている。レボドパはパーキンソン病に最も有効な治療薬であるが、ウェアリング・オフやレボドパ誘発ジスキネジアといった運動合併症が治療上の最大の問題点である。根治療法が未開発の現在、レボドパ治療を最適化することがパーキンソン病治療において最も重要である。本研究の成果はレボドパ誘発ジスキネジアの病態機序の全容解明に寄与するものであった。さらにジスキネジアの治療法のいくつかを動物モデルにおいて検討した。今後ジスキネジアの病態機序に基づいた治療を実用化することができれば、パーキンソン病治療を進歩させることができる。
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