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In vivo imaging for pathological substance and neuroinflammation/neuroactivity and therapeutic strategy in Alzheimer's disease

Research Project

Project/Area Number 17H04247
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Ouchi Yasuomi  浜松医科大学, 光尖端医学教育研究センター, 教授 (40436978)

Co-Investigator(Kenkyū-buntansha) 横倉 正倫  浜松医科大学, 医学部, 助教 (00529399)
武内 智康  浜松医科大学, 光尖端医学教育研究センター, 特任助教 (20754188)
和久田 智靖  浜松医科大学, 医学部附属病院, 講師 (80444355)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsアルツハイマー病 / 脳神経画像 / 脳・神経
Outline of Final Research Achievements

We tried to develop an imaging method using a molecular probe which produced an MRI signal for FKN and a radioisotope (RI) probe for CB2, in order to establish a new in vivo imaging technique to visualize pathological substances and M2-type neuroinflammation along with neuronal survival and synapse density in the living brain of Alzheimer’s disease (AD). The MRI signal was found to be too small possibly because the degree of the probe entering into the cell was insufficient, which might require much higher magnetic field MRI machine. In contrast, the RI probe successfully allowed imaging of M2-type cell by targeting CB2 receptor in vivo. The activation of M2 like neuroinflammation was shown to precede M1 activation at an early stage of AD model (senescence-accelerated mouse prone 10, the line of mice generating amyloid and neuronal loss). The result provided a therapeutic contention that persisting M2 activity might be a beneficial in tempering the progression of AD

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病(AD)の脳内でミクログリア活性が上昇し、その活性の強さはアミロイド蛋白(Aβ)の蓄積程度と逆相関があることを報告した。弧発性ADモデルマウス(SAMP8)でAβ出現前に神経新生が促進され、ミクログリア活性の保護性刺激が神経新生を促すことが報告された。そのためAD発症後のAβ標的療法だけでなく、ADの予防や進行抑制にAβ発現に伴う神経新生の促進と活性化ミクログリアへの介入が重要であると考えられた。本研究では、ADモデルマウスでM2系ミクログリア活性の活性化とAβの関与がわかり、AD治療ターゲットを異常蛋白以外にも視点を向ける重要性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (21 results)

All 2019 2018 2017

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 6 results) Presentation (8 results) (of which Int'l Joint Research: 6 results,  Invited: 4 results)

  • [Journal Article] Endogenous dopamine release under transcranial direct-current stimulation governs enhanced attention: a study with positron emission tomography2019

    • Author(s)
      Fukai Mina、Bunai Tomoyasu、Hirosawa Tetsu、Kikuchi Mitsuru、Ito Shigeru、Minabe Yoshio、Ouchi Yasuomi
    • Journal Title

      Translational Psychiatry

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41398-019-0443-4

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biopathological Significance of Early-Phase Amyloid Imaging in the Spectrum of Alzheimer’s Disease2019

    • Author(s)
      Bunai Tomoyasu、Kakimoto Akihiro、Yoshikawa Etsuji、Terada Tatsuhiro、Ouchi Yasuomi
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 69 Issue: 2 Pages: 529-538

    • DOI

      10.3233/jad-181188

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer's disease.2019

    • Author(s)
      Terada T, Yokokura M, Obi T, Bunai T, Yoshikawa E, Ando I, Shimada H, Suhara T, Higuchi M, Ouchi Y.
    • Journal Title

      J Neurol.

      Volume: 266(9) Issue: 9 Pages: 2186-2196

    • DOI

      10.1007/s00415-019-09400-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alterations in serotonin transporter and body image-related cognition in anorexia nervosa2019

    • Author(s)
      Yokokura Masamichi、Terada Tatsuhiro、Bunai Tomoyasu、Nakaizumi Kyoko、Kato Yasuhiko、Yoshikawa Etsuji、Futatsubashi Masami、Suzuki Katsuaki、Yamasue Hidenori、Ouchi Yasuomi
    • Journal Title

      NeuroImage: Clinical

      Volume: 23 Pages: 101928-101928

    • DOI

      10.1016/j.nicl.2019.101928

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of Cannabinoid Receptor Type 2, but Not TSPO, in Senescence-Accelerated Neuroinflammation in Mice: A Positron Emission Tomography Study2019

    • Author(s)
      Satoru Yamagishi, Yurika Iga, Masato Nakamura, Chika Takizawa, Dai Fukumoto, Takeharu Kakiuchi, Shingo Nishiyama, Hiroyuki Ohba, Hideo Tsukada, Kohji Sato, Yasuomi Ouchi
    • Journal Title

      J Neuroinflammation .

      Volume: 16 Issue: 1 Pages: 208-208

    • DOI

      10.1186/s12974-019-1604-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo depiction of α7 nicotinic receptor loss for cognitive decline in Alzheimer’s disease2018

    • Author(s)
      Nakaizumi K, Ouchi Y, Terada T, Yoshikawa E, Kakimoto A, Isobe T, Bunai T, Yokokura Y, Suzuki K, Magata Y
    • Journal Title

      J Alzheimers Dis

      Volume: 61 Issue: 4 Pages: 1355-1365

    • DOI

      10.3233/jad-170591

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroinflammation following disease modifying therapy in multiple sclerosis A pilot positron emission tomography study2018

    • Author(s)
      Bunai T, Terada T, Kono S, Yokokura M, Yoshikawa E, Futatsubashi M, Miyajima H, Ouchi Y
    • Journal Title

      J Neurol Sci

      Volume: 385 Pages: 30-33

    • DOI

      10.1016/j.jns.2017.12.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Similar neural correlates of planning and execution to inhibit continuing actions2018

    • Author(s)
      Omata K, Ito S, Takata Y, Ouchi Y
    • Journal Title

      Front Neurosci

      Volume: 12 Pages: 951-960

    • DOI

      10.3389/fnins.2018.01024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Lateral Occipito-temporal Cortex Is Involved in the Mental Manipulation of Body Part Imagery2017

    • Author(s)
      Kikuchi Mitsuru、Takahashi Tetsuya、Hirosawa Tetsu、Oboshi Yumi、Yoshikawa Etsuji、Minabe Yoshio、Ouchi Yasuomi
    • Journal Title

      Front Hum Neurosci.

      Volume: 11 Pages: 1-11

    • DOI

      10.3389/fnhum.2017.00181

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] pilot study of serotonergic modulation after long-term administration of oxytocin in autism spectrum disorder.2017

    • Author(s)
      Hirosawa T, Kikuchi M, Ouchi Y, Takahashi T, Yoshimura Y, Kosaka H, Furutani N, Hiraishi H, Fukai M, Yokokura M, Yoshikawa E, Bunai T, Minabe Y.
    • Journal Title

      Autism Res.

      Volume: - Issue: 5 Pages: 113-117

    • DOI

      10.1002/aur.1761

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxytocin effects on emotional response to others’ faces via serotonin system in autism: A pilot study2017

    • Author(s)
      Fukai Mina、Hirosawa Tetsu、Kikuchi Mitsuru、Ouchi Yasuomi、Takahashi Tetsuya、Yoshimura Yuko、Miyagishi Yoshiaki、Kosaka Hirotaka、Yokokura Masamichi、Yoshikawa Etsuji、Bunai Tomoyasu、Minabe Yoshio
    • Journal Title

      Psychiatry Res.

      Volume: 267 Pages: 45-50

    • DOI

      10.1016/j.pscychresns.2017.06.015

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reversible amygdala enlargement: a longitudinal observation of a patient with elderly onset temporal lobe epilepsy2017

    • Author(s)
      Matsudaira Takashi、Omote Yoshio、Terada Tatsuhiro、Kondo Akihiko、Obi Tomokazu、Ouchi Yasuomi、Inoue Yushi
    • Journal Title

      J Neurol

      Volume: 264 Issue: 12 Pages: 2487-2490

    • DOI

      10.1007/s00415-017-8649-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imaging neuroinflammation to monitor α-synucleinopathy.2017

    • Author(s)
      Ouchi Y
    • Journal Title

      Lancet Neurol.

      Volume: 16 Issue: 10 Pages: 763-764

    • DOI

      10.1016/s1474-4422(17)30244-2

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] In vivo depiction of alpha-7 nicotinic receptors in the Meynert nucleus in aging vs. dementia2019

    • Author(s)
      1.Yasuomi Ouchi, Kyoko Nakaizumi, Tatsuhiro Terada, Tomoyasu Bunai, Etsuji Yoshikawa, Yasuhiro Magata
    • Organizer
      第60回日本神経学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] In vivo imaging of neuroinflammation associated with misfolded proteins in Alzheimer’s disease.2019

    • Author(s)
      Yasuomi Ouchi
    • Organizer
      29th International Society for Cerebral Blood Flow and Metabolism
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo imaging of mitochondrial activity in the human brain for elucidating the pathophysiology of dementia2019

    • Author(s)
      Yasuomi Ouchi
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Clinicopathophysiology of α7 nicotinic receptor in Meynert cholinergic regions in aging and dementia2018

    • Author(s)
      Yasuomi Ouchi, Tatsuhiro Terada, Kyoko Nakaizumi, Etsuji Yoshikawa, Tomoyasu Bunai, Yasuhiro Magata
    • Organizer
      第24回Annual Meeting of the Organization for Human Brain Mapping
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The increase of dopamine transporter density in the ventral striatum and its correlation with motor improvement in patients with Parkinson’s disease after subthalamic nucleus deep brain stimulation2018

    • Author(s)
      Takao Nozaki, Kenji Sugiyama, Tetsuya Asakawa, Hiroki Namba, Masamichi Yokokura2 Tetuhiro Terada, Yasuomi Ouchi
    • Organizer
      European Society for Stereotactic and Functional Neurosurgery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Differences in TSPO and cannabinoid receptor CB2 binding at an early stage in poststroke neuroinflammation in living rats.2017

    • Author(s)
      Ouchi Y, Fukumoto D, Kakiuchi T, Nishiyama S, Yamamoto S, Ohba H, Hosoya T, Tsukada H
    • Organizer
      第18回Brain/BrianPET
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo imaging of mitochondrial complex CM-1 in the human brain.2017

    • Author(s)
      Yasuomi Ouchi, Tatsuhiro Terada, Masami Futatsubashi, Bunai Tomoyasu, Masamichi Yokokura, Etsuji Yoshikawa, Hideo Tsukada.a
    • Organizer
      第23回Annual Meeting of the Organization for Human Brain Mapping
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Yasuomi Ouchi. In vivo depiction of neuroinflammation on the cholinergic system and cognition in humans.2017

    • Author(s)
      Michi Y
    • Organizer
      第13回 Internatioinal symposium of geriatirics and gerontology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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