분자영상 및 방사화학

본문글자크기
  • 2021년 07월호
    [Cells.] TSPO Expression Modulatory Effect of Acetylcholinesterase Inhibitor in the Ischemic Stroke Rat Model 허혈성 뇌졸중 쥐 모델에서 Acetylcholinesterase 억제제의 TSPO 발현 조절 효과

    서울대 / 송유성, 이상희, 이병철*, 김상은*

  • 출처
    Cells.
  • 등재일
    2021 May 29
  • 저널이슈번호
    10(6):1350. doi: 10.3390/cells10061350.
  • 내용

    바로가기  >

    Abstract
    We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.

     

     

    Affiliations

    Yoo Sung Song  1 , Sang Hee Lee  1   2 , Jae Ho Jung  1 , In Ho Song  1 , Hyun Soo Park  1 , Byung Seok Moon  3 , Sang Eun Kim  1   4   5 , Byung Chul Lee  1   5
    1 Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea.
    2 Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
    3 Department of Nuclear Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul 07804, Korea.
    4 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Korea.
    5 Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Korea.

  • 키워드
    acetylcholinesterase; ischemia; middle cerebral artery occlusion; neuroinflammation; positron emission tomography; radioligands; translocator protein 18-kDa.
  • 연구소개
    기존의 아세틸콜린에스터라제(acetylcholinesterase, AChE) 억제제의 사용은 치매 및 뇌졸중환자를 대상으로 인지 기능 향상에만 관여하는 것으로 알려져 있음. 본 연구에서는 전이체 단백질(translocator proteins, TSPO)과 AChE에 특이적인 서로 다른 PET 프로브([18F]fluoromethyl-PBR28-d2 & 3-[18F]F-CP118,954)를 이용하여, AChE 활성이 뇌에서의 염증 반응 초기 과정에서 상승되고 뒤이어 TSPO 활성이 뇌의 허혈 후 손상 전반에 걸쳐 지속적으로 상승한다는 것을 동일한 뇌졸중 동물모델에서 두 가지의 PET 영상을 통해 확인하였음. 이를 통해 신경전달물질인 아세틸콜린은 초기 신경염증 과정에 참여한 후에 소교세포 활성화(microglial activation)를 촉발 한 후 기본 상태로 돌아감을 관찰하였고, 대표적인 AChE 억제제인 도네페질(donepezil)이 신경 독성 염증 반응을 억제하거나 지연시키는 치료 옵션으로 작용할 수 있음을 제안함.
  • 편집위원

    이 논문은 동물모델을 이용한 3-[18F]F-CP118,954를 이용한 AChE (acetylcholinesterase)표적 PET 영상과 [18F]fluoromethyl-PBR28-d2를 이용한 18 kDa TSPO (translocator protein)표적 PET 영상에 대한 연구이다. 결과적으로, MCAO(middle cerebral artery occlusion) Spague-Dawley rat 동물모델을 이용하여 뇌졸중 후 염증성 뇌 반응 과정을 AChE / TSPO PET 영상을 통해 확인할 수 있었다.

    덧글달기2021-06-30 16:13:41

  • 덧글달기
    덧글달기
       IP : 13.58.36.141

    등록