Development of analytical technology of pathological protease activity based on MRI, and its application for the prevention of schizophrenia

• Project/Area Number: 16K10220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagoya City University
• Principal Investigator: Ueki Takatoshi 名古屋市立大学, 大学院医学研究科, 教授 (60317328)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 神経免疫系 / 統合失調症 / 脳内免疫細胞 / ミクログリア / 脳神経疾患

Outline of Final Research Achievements

In the present study the investigators aim at exploring the neuropathology underlying microglial activation in the brain in the early stage of onset of schizophrenia, and development of in vivo MRI system to visualize behavior of microglia. Here, based on the observation that processing of fractalkine in the adjacent neuronal axon triggers microglial activation via its membranous CRXCR3 receptor, the pathophysiology of the activation of metabolic enzyme of neuronal fractalkine was explored and also MRI switching molecular probe to visualize the enzymatic activity was developed.

Academic Significance and Societal Importance of the Research Achievements

統合失調症は、多因子疾患であり、症候群 である。これまでに、統合失調症患者での MRI(磁気共鳴画像法)による脳構造解析の 結果、脳局所での容積変化が報告される等、統合失調 症患者で健常人との有為差が認められてい るが、個々の因子は、患者間での標準偏差 が大きく、それらを統合失調症の診断のた めの指標とすることは困難である。対して、 活性化ミクログリアの著明な増加は、未治 療の統合失調症患者の全てにおいて認めら れる現象であり、統合失調症患者と健常人 とを識別するのに極めて有用な指標である と考えられる。

Research Products

• [Int'l Joint Research] Morehouse School of Medicine(米国)
• [Journal Article] Potential implication of SGK1-dependent activity change in BV-2 microglial cells. (2018)
  • Author(s): Asai H, Inoue K, Sakura E, Shinohara Y, Ueki T.
  • Journal Title: Int J Physiol Pathophysiol Pharmacol Volume: 10 Pages: 115-123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivo TSPO and cannabinoid receptor type 2 availability early in poststroke neuroinflammation in rats: a positron emission tomography study study. (2017)
  • Author(s): Hosoya T, Fukumoto D, Kakiuchi T, Nishiyama S, Yamamoto S, Ohba H, Tsukada H, Ueki T, Sato K, Ouchi Y.
  • Journal Title: J Neuroinflammation. Volume: 29 Issue: 1 Pages: 69-78
  • DOI: 10.1186/s12974-017-0851-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1. (2016)
  • Author(s): Fujitsuka N, Asakawa A, Morinaga A, Amitani MS, Amitani H, Katsuura G, Sawada Y, Sudo Y, Uezono Y, Mochiki E, Sakata I, Sakai T, Hanazaki K, Yada T, Yakabi K, Sakuma E, Ueki T, Niijima A, Nakagawa K, Okubo N, Takeda H, Asaka M, Inui A.
  • Journal Title: Mol Psychiatry Volume: 21 Issue: 11 Pages: 1-11
  • DOI: 10.1038/mp.2015.220
  • Peer Reviewed / Open Access
• [Journal Article] Role of serum- and glucocorticoid-inducible kinases in stroke. (2016)
  • Author(s): Inoue K, Leng T, Yang T, Zeng Z, Ueki T, Xiong ZG.
  • Journal Title: J Neurochem. Volume: 138 Issue: 2 Pages: 354-361
  • DOI: 10.1111/jnc.13650
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum- and glucocorticoid-inducible kinases in microglia. (2016)
  • Author(s): Inoue K, Sakuma E, Morimoto H, Asai H, Koide Y, Leng T, Wada I, Xiong ZG, Ueki T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 478 Issue: 1 Pages: 53-59
  • DOI: 10.1016/j.bbrc.2016.07.094
  • Peer Reviewed / Open Access / Int'l Joint Research