Development of in vivo molecular imaging system to analyze microglial behavior in the brain, and its application for early diagnosis of schizophrenia

• Project/Area Number: 15H04273
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Sato Kohji 浜松医科大学, 医学部, 教授 (80235340)
• Co-Investigator(Kenkyū-buntansha): 植木 孝俊 名古屋市立大学, 大学院医学研究科, 教授 (60317328) ; 森 則夫 浜松医科大学, 医学部, 教授 (00174376)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 統合失調症 / 脳神経疾患 / 神経免疫系

Outline of Final Research Achievements

The investigators previously found microglia is aberrantly activated in the brain of schizophrenic patients by positron emission tomography. 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.

Research Products

• [Journal Article] Potential implication of SGK1-dependent activity change in BV-2 microglial cells (2018)
  • Author(s): Hayato Asai, Koichi Inoue, Eisuke Sakuma, Yoshiaki Shinohara, Takatoshi Ueki
  • Journal Title: Int J Physiol Pathophysiol Pharmacol Volume: -
  • Peer Reviewed / 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] 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
• [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] 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