Origin of crosstalk between brain and blood immune cells in Parkinson's disease and its involvement in pathology

• Project/Area Number: 17K09783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Sapporo Medical University
• Principal Investigator: Suzuki Syuuichirou 札幌医科大学, 医学部, 講師 (90532929)
• Co-Investigator(Kenkyū-buntansha): 下濱 俊 札幌医科大学, 医学部, 教授 (60235687)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: パーキンソン病 / 免疫細胞 / ミクログリア / 神経細胞死 / 骨髄キメララット / 脳神経疾患 / 6-OHDA / GFP

Outline of Final Research Achievements

Parkinson's disease (PD) is a neurodegenerative disease for which there is no underlying cure, and there are many indications about its pathogenic mechanism but it has not been identified. Recent nuclear medicine technology showed that activation of microglia (MG) and migration of lymphocytes into the brain were confirmed in the substantia nigra of the PD patient's brain, and their involvement in the pathological condition has attracted attention. We obtained data suggesting that intravascular immune cells are greatly involved in the pathogenesis of PD in studies using PD animal models. To prove this, we succeeded in producing GFP bone marrow chimeric PD rats capable of distinguishing MG and peripheral macrophages with overlapping gene profiles. Furthermore, it was confirmed that intravascular immune cells were transferred to the substantia nigra region of the rat model.

Academic Significance and Societal Importance of the Research Achievements

PDに限らず神経変性疾患の原因は当然神経やグリアにあるとされ研究が進められてきたが、本研究の特色としてPDの病態形成を血管内の免疫細胞に着目し原因を探索することがあげられる。本研究で得た新知見によりPD発症前の血液バイオマーカーの発見に繋がり、発症予防や早期治療の開始時期が提言できる可能性がある。
この研究手法がアルツハイマー病や筋萎縮性側索硬化症など病態形成に炎症の関与が指摘される他の神経変性疾患にも応用できる可能性がある。本研究の着眼点と研究手法が神経変性疾患だけでなく、他の加齢性疾患の病態解明にも応用され、免疫細胞の関与が発見される可能性もあり重要な意義がある。

Research Products

• [Presentation] Immunohistological study of immunocytes in 6-OHDA-induced lesion in a rat Parkinson's disease model. (2020)
  • Author(s): 鈴木 秀一郎, 鈴木 紘美、齋藤 太郎、横川 和樹、真部 建郎、松下 隆司、松村 晃寛、久原 真、下濱 俊
  • Organizer: 第61回日本神経学会学術大会
• [Presentation] Time course of intranigral invasion of immunocytes in 6-OHDA-induced Parkinson's disease rat model. (2019)
  • Author(s): 鈴木 紘美、齋藤 太郎、横川 和樹、藤倉 舞、真部 健郎、岩原 直敏、松下 隆司、松村 晃寛、久原 真、川又 純、下濱 俊
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] Intracerebral infiltration of immune cells in 6-OHDA-induced Parkinson's disease model rat. (2018)
  • Author(s): 鈴木秀一郎、鈴木紘美、蒲生直希、齋藤太郎、横川和樹、藤倉舞，真部建郎、岩原直敏、松村晃寛、松下隆司、久原真、川又純、下濱俊
  • Organizer: 第59回日本神経学会学術大会
• [Presentation] The optimal preconditioning for bone marrow transplantation to establish 6-OHDA-lesioned GFP bone marrow chimeric PD model rat. (2018)
  • Author(s): Syuuichirou Suzuki, Hiromi Suzuki, Taro Saito, Kazuki Yokokawa, Mai Fujikura, Tatsuo Manabe, Naotoshi Iwahara, Akihiro Matsumura, Takashi Matsushita, Shin Hisahara, Jun Kawamata, Miho Emoto, Shun Shimohama
  • Organizer: 第23回世界神経学会議(WCN2017)
• [Presentation] THE OPTIMAL PRECONDITIONING FOR BONE MARROW TRANSPLANTATION TO ESTABLISH 6-OHDA-LESIONED GFP BONE MARROW CHIMERIC PD MODEL RAT. (2017)
  • Author(s): S Suzuki, H Suzuki, K Yokokawa,T Saito, M Fujikura, T Manabe, N Iwahara, A Matsumura, T Matsushita, S Hisahara, J Kawamata, S Shimohama
  • Organizer: World Congress of Neurology 2017
  • Int'l Joint Research