Glial-mediated abnormal neuroplasticity in levodopa-induced dyskinesia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Osaka University
• Principal Investigator: Baba Kousuke 大阪大学, 大学院医学系研究科, 招へい教員 (90750159)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: パーキンソン病 / αシヌクレイン / ドパミン神経変性 / バイオマーカー

Outline of Final Research Achievements

To elucidate the pathogenesis of levodopa-induced dyskinesia, a late motor complication of Parkinson's disease (PD), we first analyzed the state of dopamine neurons in the prodromal phase before dopamine neurodegeneration. We performed RNAseq analyses of dopaminergic neurons in the substantia nigra (SN) of a PD mouse model in the prodromal stage. As a result, we observed that many gene expressions are altered before dopaminergic neurodegeneration occurs. Among these, we analyzed gene X, which has not been previously implicated in PD. We confirmed that α-synuclein fibril inoculation induces gene X expression in the SN dopaminergic neurons of mice. We also confirmed that gene X is upregulated in the SN dopaminergic neurons of PD patients. Furthermore, we established a measurement system using biological samples from human PD patients.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

本研究課題でこれまでパーキンソン病との関連が指摘されていなかったgene XがPDマウスモデルでドパミン神経変性が起こる前に発現上昇することを見出した。これはPDにおける緩徐進行性のドパミン神経変性の分子機序を解明する足掛かりとなりうる。更に、ドパミン神経変性前に発現上昇するだけでなく、ヒトPD患者の死後脳サンプルでも発現上昇が確認された。これはPDにおける新たなバイオマーカーの開発につながる可能性があり大きな学術的、社会的意義を有する。