The roles of cyclooxygenase-1 in microglial activation

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790269
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: 独立行政法人国立精神・神経医療研究センター
• Principal Investigator: SHUKURI Miho 独立行政法人国立精神・神経医療研究センター, 脳病態統合イメージングセンター, 流動研究員 (20525571)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: シクロオキシゲナーゼ / PET / 神経炎症 / 神経障害

Research Abstract

Previously, we reported that ¹¹C-labeled ketoprofen-methyl ester (KTP-Me), a derivative of COX-1 selective inhibitor, could visualize the activation of microglia in rat model of neuroinflammation. In order to assess the hypothesis that COX-1 may play a crucial role in neuroinflammation, we evaluated the involvement of COX-1 in neuronal damages after transient middle cerebral artery occlusion (t-MCAO) in mice and rats. PET images with [¹¹C]KTP-Me were well correlated with the time-dependent changes of activated microglia in ischemic region after t-MCAO. The studies using COX-1 knockout mice revealed that the deficiency of COX-1 reduced neuroinflammation but exacerbated neurotoxicity induced by t-MCAO. These results raise the possibility that COX-1 may be involved in the neuroprotective functions after focal cerebral ischemia.

Research Products

• [Journal Article] 神経炎症におけるシクロオキシゲナーゼのPET分子イメージング (2014)
  • Author(s): 宿里充穂, 尾上浩隆
  • Journal Title: 医学のあゆみ Volume: 248 Pages: 907-911
• [Journal Article] アルツハイマー病の治療薬、イメージング剤としてのNSAIDsの可能性 (2013)
  • Author(s): 宿里充穂, 尾上浩隆
  • Journal Title: PETジャーナル Volume: 21 Pages: 10-12
• [Journal Article] Assessment of radioligands for PET imaging of cyclooxygenase-2 in an ischemic neuronal injury model (2013)
  • Author(s): Ji B, Kumata K, Onoe H, Kaneko H, Zhang MR, Seki C, Ono M, Shukuri M, Tokunaga M, Minamihisamatsu T, Suhara T, Higuchi M
  • Journal Title: Brain Res Volume: 1533 Pages: 152-62
  • DOI: 10.1016/j.brainres.2013.08.026
  • Peer Reviewed
• [Journal Article] The food reaching test : a sensitive test of behavioral improvements by deep brain stimulation in MPTP-treated monkey (2012)
  • Author(s): Asakawa T, Sugiyama K, Akamine S, Yokoyama C, Shukuri M, Mizuma H, Tsukada H, Onoe H, Namba H
  • Journal Title: Neurosci Res Volume: 74(2) Pages: 122-8
  • DOI: 10.1016/j.neures.2012.07.006
  • Peer Reviewed
• [Journal Article] Human whole-body biodistribution and dosimetry of a new PET tracer
  • Author(s): Ohnishi A, Senda M, Yamane T, Sasaki M, Mikami T, Nishio T, Ikari Y, Nishida H, Shukuri M, Takashima T, Mawatari A, Doi H, Watanabe Y, Onoe H
  • Journal Title: [^<11>C] ketoprofen methyl ester, for imagings of neuroinflammation Volume: (in press)
  • DOI: 10.1016/j.nucmedbio.2014.04.008
  • Peer Reviewed
• [Presentation] Novel PET probe targeting cyclooxygenase for imaging microglial activation (2013)
  • Author(s): Shukuri M
  • Organizer: The 6^<th> CJK Conference on Nuclear Medicine
  • Place of Presentation: Haevichi Hotel, Jeju Korea
  • Year and Date: 20131115-17
  • Invited
• [Presentation] 神経炎症の分子イメージング (2013)
  • Author(s): 宿里充穂
  • Organizer: PETサマーセミナー
  • Place of Presentation: ホテル日航金沢, 石川県
  • Year and Date: 20130823-25
  • Invited
• [Presentation] Evaluation of ^<11>C-ketoprofen-methyl ester as a potent (2012)
  • Author(s): Shukuri M, Takashima T, Takashima -Hirano M, Mawatari A, Yamanaka H, Katayama Y, Doi H, Suzuki M, Watanabe Y, Onoe H
  • Organizer: PET probe for cyclooxygenase imaging
  • Place of Presentation: Milano Congressi, Milano Italy
  • Year and Date: 20121027-31
• [Presentation] げっ歯類および霊長類サルを用いた [^<11>C] Ketoprofen-methyl esterの特性評価 (2012)
  • Author(s): 宿里充穂, 高島忠之, 馬渡彩, 山中創, 片山由美子, 川崎章弘, 土居久志, 鈴木正昭, 渡辺恭良, 千田道雄, 尾上浩隆
  • Organizer: 第52回日本核医学会学術総会
  • Place of Presentation: ロイトン札幌, 北海道
  • Year and Date: 20121011-13
• [Presentation] 脳虚血再灌流モデルにおける [^<11>C] Ketoprofen-methyl esterによるCOX-1イメージング (2012)
  • Author(s): 宿里充穂, 馬渡彩, 大野正裕, 高島好聖, 土居久志, 鈴木正昭, 渡辺恭良, 尾上浩隆
  • Organizer: 第52回日本核医学会学術総会
  • Place of Presentation: ロイトン札幌, 北海道
  • Year and Date: 20121011-13