Elucidation for a role of kynurenine pathway on the pathogenesis of depression

• Project/Area Number: 25460114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: Maeda Jun 国立研究開発法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (30415426)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: トリプトファン / キヌレニン / 陽電子断層撮像 / うつ病 / ストレス / セロトニン / てんかん / PET / 認知症 / 炎症 / 脳 / 膵臓 / 糖質コルチコイド / アミノ酸トランスポーター

Outline of Final Research Achievements

To visualize an incorporation efficiency of tryptophan, a tryptophan analogue [11C]1-methyl-L-tryptopan was synthesized with positron labeling, and the characterization of [11C]1-MT bio-distribution in rodents was investigated using small-animal PET. The uptake of [11C]1-MT in the pancreas was the highest concentration among the organs, while the other organs were relative lower concertation compared to the pancreas. The uptakes of [11C]1-MT in the brain and pancreas were in an active manner, and pretreatment with corticosteroid decreased the cerebral and pancreatic uptakes of [11C]1-MT by 30 %. These results suggested that the uptake of [11C]1-MT was dependent on tryptophan metabolism induced by stress, and indicated that [11C]1-MT was a beneficial marker for diagnosis of depression.

Research Products

• [Journal Article] Development of TASP0410457 (TASP457), a novel dihydroquinolinone derivative as a PET radioligand for central histamine H3 receptors (2016)
  • Author(s): Kazumi Koga, Jun Maeda, Masaki Tokunaga, Masayuki Hanyu, Kazunori Kawamura, Mari Ohmichi, Toshio Nakamura, Yuji Nagai, Chie Seki, Yasuyuki Kimura, Takafumi Minamimoto, Ming-Rong Zhang, Toshimitsu Fukumura, Tetsuya Suhara, Makoto Higuchi
  • Journal Title: EJNMMI Research Volume: 6 Issue: 1 Pages: 1-14
  • DOI: 10.1186/s13550-016-0170-2
  • Peer Reviewed / Open Access
• [Journal Article] Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and behavioral phenotypes related to schizophrenia. (2013)
  • Author(s): Takao K, Kobayashi K, Hagihara H, Ohira K, Shoji H, Hattori S, Koshimizu H, Umemori J, Toyama K, Nakamura HK, Kuroiwa M, Maeda J, Atsuzawa K, Esaki K, Yamaguchi S, Furuya S, Takagi T, Walton NM, Hayashi N, Suzuki H, Higuchi M, Usuda N, Suhara T, Nishi A, Matsumoto M, Ishii S, Miyakawa T.
  • Journal Title: Neuropsychopharmacology Volume: 38(8) Issue: 8 Pages: 1409-25
  • DOI: 10.1038/npp.2013.38
  • Peer Reviewed / Open Access
• [Presentation] コカインによるドーパミントランスポーター占有率と細胞外ドーパミン濃度の関係性 (2014)
  • Author(s): 前田 純、関 千絵、南久松丈晴、張 明栄、樋口 真人、須原 哲也
  • Organizer: 第24回日本臨床精神神経薬理学会 第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-20 – 2014-11-21
• [Presentation] [11C]1-Methyl-L-tryptophanによる脳および膵臓のL-tryptophan利用能の測定 (2014)
  • Author(s): 前田純、熊田勝志、張明栄、徳永正希、南久松丈晴、関千江、樋口真人、須原哲也
  • Organizer: 第54回日本核医学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-06
• [Presentation] PET Imaging of glial activation and neuroinflammation in dementia and other neurological disorders by translocator protein (TSPO) ligands (2013)
  • Author(s): Jun Maeda
  • Organizer: Joint Research Projects/Seminars NSFC-JSPS (China-Japan)
  • Place of Presentation: 上海
  • Invited
• [Remarks] MONI
  • URL: http://www.nirs.go.jp/seika/brain/
• [Remarks] MONI
  • URL: http://www.nirs.go.jp/seika/brain/