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Multi-layer illustration of neuronal viability and microglial polarization in Alzheimer's disease

Research Project

Project/Area Number 20H03600
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52030:Psychiatry-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Yasuomi Ouchi  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, 医学部附属病院, 助教 (20754188)
亀野 陽亮  浜松医科大学, 医学部, 助教 (40537255)
和久田 智靖  浜松医科大学, 医学部附属病院, 講師 (80444355)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2021: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsアルツハイマー病
Outline of Research at the Start

早期アルツハイマー病(AD)の脳内で主に傷害性ミクログリア(M1性)の活性化が生じていること、その程度がタウ(tau)の脳内蓄積と関連している。ADはアミロイド(Aβ)やtauなどの異常蛋白の生成が生じているため、早期からM1ミクログリア活性が有意であることも示唆されている。本研究では、ミクログリア極性のM1極性からM2極性変化を捉え、細胞死に関与するミトコンドリア活性変化を同時に可視化する生体画像化を実現し、ミクログリアと神経・シナプス細胞死を捉える多角的な画像評価系を創出する。

Outline of Final Research Achievements

We evaluated the neuronal viability and investigated the relation between microglial polarization M1M2 and the neuronal viability in the brain of Alzheimer's disease (AD). A cell line examination with V2 and the MG5 cells and PET metabolic probes showed that oxidate metabolism is dominant in the state of the M2 polarized condition than the M1 condition. A PET probe [11C]NE40 that can evaluate the M2 state accumulated more and [18F]BCPP-EF probe for mitochondrial activity increased more in early dementia model mice. A treatment that activates mitochondrial activity reduced the degree of M1 response. In this project, although no ideal probe for microglia M2 polarization was developed, a combined index (reduction of M1 polarity and increase in mitochondrial activity) may be a useful outcome to understand the brain environment of AD before medical intervention.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病の脳内ではアミロイドなど病変蛋白の出現により脳内環境は複雑である。神経炎症でも障害性と保護性のグリア細胞活動が生じている。治療戦略を立てるときにどのような状態かを把握する必要がある。保護性ミクログリアを可視化しそれを刺激することで神経細胞を生かすことができれば治療上のメリットは計り知れない。今回の成果で、神経生存を高めることで、M1神経障害性のミクログリア活動を減らすことができる可能性をin vivo画像で示した。この画像的特徴(M1活性減少・神経ミトコンドリア活動上昇)を治療の有益性指標とできる可能性を示すことで、今後開発されるAD治療薬を評価することができると期待された。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (26 results)

All 2023 2022 2021 2020

All Journal Article (19 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 19 results,  Open Access: 10 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results)

  • [Journal Article] Lower Availability of Mitochondrial Complex I in Anterior Cingulate Cortex in Autism: A Positron Emission Tomography Study2023

    • Author(s)
      Kato Yasuhiko、Yokokura Masamichi、Iwabuchi Toshiki、Murayama Chihiro、Harada Taeko、Goto Takafumi、Tamayama Taishi、Kameno Yosuke、Wakuda Tomoyasu、Kuwabara Hitoshi、Benner Seico、Senju Atsushi、Tsukada Hideo、Nishizawa Sadahiko、Ouchi Yasuomi、Yamasue Hidenori
    • Journal Title

      American Journal of Psychiatry

      Volume: 180 Issue: 4 Pages: 277-284

    • DOI

      10.1176/appi.ajp.22010014

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain <scp>p3‐Alcβ</scp> peptide restores neuronal viability impaired by Alzheimer's amyloid β‐peptide2023

    • Author(s)
      Hata S, Saito H, Kakiuchi T, Fukumoto D, Yamamoto S, Kasuga K, Kimura A, Moteki K, Abe R, Adachi S, Kinoshita S, Yoshizawa-Kumagaye K, Nishio H, Saito T, Saido TC, Yamamoto T, Nishimura M, Taru H, Sobu Y, Ohba H, Nishiyama S, Harada N, Ikeuchi T, Tsukada H, Ouchi Y, Suzuki T
    • Journal Title

      EMBO Molecular Medicine

      Volume: - Issue: 5 Pages: 1-15

    • DOI

      10.15252/emmm.202217052

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mitochondrial complex I abnormalities underlie neurodegeneration and cognitive decline in Alzheimer’s disease2022

    • Author(s)
      Terada Tatsuhiro、Therriault Joseph、Kang Min Su、Savard Melissa、Pascoal Tharick Ali、Lussier Firoza、Tissot Cecile、Wang Yi‐Ting、Benedet Andrea、Poltronetti Nina Margherita、Ottoy Julie、Arias Jaime、Frenandez、Bezgin Gleb、Matsudaira Takashi, et al.
    • Journal Title

      European Journal of Neurology

      Volume: 29 Issue: 5 Pages: 1324-1334

    • DOI

      10.1111/ene.15246

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Extrastriatal dopamine D2/3 receptor binding, functional connectivity, and autism socio-communicational deficits: a PET and fMRI study2022

    • Author(s)
      Murayama C, Iwabuchi T, Kato Y, Yokokura M, Harada T, Goto T, Tamayama T, Kameno Y, Wakuda T, Kuwabara H, Senju A, Nishizawa S, Ouchi Y, Yamasue H.
    • Journal Title

      Mol Psychiatry

      Volume: - Issue: 4 Pages: 2106-2113

    • DOI

      10.1038/s41380-022-01464-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo Illustration of Altered Dopaminergic and GABAergic Systems in Early Parkinson's Disease2022

    • Author(s)
      Takashima Hirotsugu、Terada Tatsuhiro、Bunai Tomoyasu、Matsudaira Takashi、Obi Tomokazu、Ouchi Yasuomi
    • Journal Title

      Frontiers in Neurology

      Volume: 13

    • DOI

      10.3389/fneur.2022.880407

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep-learning prediction of amyloid deposition from early-phase amyloid positron emission tomography imaging2022

    • Author(s)
      Komori Seisaku、Cross Donna J.、Mills Megan、Ouchi Yasuomi、Nishizawa Sadahiko、Okada Hiroyuki、Norikane Takashi、Thientunyakit Tanyaluck、Anzai Yoshimi、Minoshima Satoshi
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 36 Issue: 10 Pages: 913-921

    • DOI

      10.1007/s12149-022-01775-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease2022

    • Author(s)
      Tatsuhiro Terada, Joseph Therriault, Min Su Peter Kang, Melissa Savard, Tharick Ali Pascoal, Firoza Lussier, Cecile Tissot, Yi-Ting Wang, Andrea Benedet, Takashi Matsudaira, Tomoyasu Bunai, Tomokazu Obi, Hideo Tsukada, Yasuomi Ouchi, Pedro Rosa-Neto
    • Journal Title

      Mol Neurodegener

      Volume: 16 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s13024-021-00448-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deep learning-based attenuation correction for brain PET with various radiotracers2021

    • Author(s)
      Hashimoto Fumio、Ito Masanori、Ote Kibo、Isobe Takashi、Okada Hiroyuki、Ouchi Yasuomi
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 35 Issue: 6 Pages: 691-701

    • DOI

      10.1007/s12149-021-01611-w

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo alterations of mitochondrial activity and amyloidosis in early-stage senescence-accelerated mice: a positron emission tomography study2021

    • Author(s)
      Yamagishi Satoru、Iga Yurika、Ikegaya Shunsuke、Kakiuchi Takeharu、Ohba Hiroyuki、Nishiyama Shingo、Fukomoto Daisuke、Kanazawa Masakatsu、Harada Norihiro、Tsukada Hideo、Sato Kohji、Ouchi Yasuomi
    • Journal Title

      Journal of Neuroinflammation

      Volume: 18 Issue: 1 Pages: 288-288

    • DOI

      10.1186/s12974-021-02343-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Corrigendum: Regional and Temporal Differences in Brain Activity With Morally Good or Bad Judgments in Men: A Magnetoencephalography Study2021

    • Author(s)
      Hiraishi Hirotoshi、Ikeda Takashi、Saito Daisuke N.、Hasegawa Chiaki、Kitagawa Sachiko、Takahashi Tetsuya、Kikuchi Mitsuru、Ouchi Yasuomi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 753147-753147

    • DOI

      10.3389/fnins.2021.753147

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased anteroventral striatal dopamine transporter and motor recovery after subthalamic deep brain stimulation in Parkinson’s disease2021

    • Author(s)
      Nozaki Takao、Sugiyama Kenji、Asakawa Tetsuya、Namba Hiroki、Yokokura Masamichi、Terada Tatsuhiro、Bunai Tomoyasu、Ouchi Yasuomi
    • Journal Title

      Journal of Neurosurgery

      Volume: 31 Issue: 2 Pages: 1-11

    • DOI

      10.3171/2021.10.jns211364

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anatomical-guided attention enhances unsupervised PET image denoising performance2021

    • Author(s)
      Onishi Yuya、Hashimoto Fumio、Ote Kibo、Ohba Hiroyuki、Ota Ryosuke、Yoshikawa Etsuji、Ouchi Yasuomi
    • Journal Title

      Medical Image Analysis

      Volume: 74 Pages: 102226-102226

    • DOI

      10.1016/j.media.2021.102226

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differences in in vitro microglial accumulation of the energy metabolism tracers [18F]FDG and [18F]BCPP-EF during LPS- and IL4 stimulation2021

    • Author(s)
      Suzuki Chie、Han Sarina、Kesavamoorthy Gandhervin、Kosugi Mutsumi、Araki Kaori、Harada Norihiro、Kanazawa Masakatsu、Tsukada Hideo、Magata Yasuhiro、Ouchi Yasuomi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13200-13200

    • DOI

      10.1038/s41598-021-92436-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] tDCS-induced modulation of GABA concentration and dopamine release in the human brain: A combination study of magnetic resonance spectroscopy and positron emission tomography2021

    • Author(s)
      Bunai Tomoyasu、Hirosawa Tetsu、Kikuchi Mitsuru、Fukai Mina、Yokokura Masamichi、Ito Shigeru、Takata Yohei、Terada Tatsuhiro、Ouchi Yasuomi
    • Journal Title

      Brain Stimulation

      Volume: 14 Issue: 1 Pages: 154-160

    • DOI

      10.1016/j.brs.2020.12.010

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease2020

    • Author(s)
      Terada T, Obi T, Bunai T, Matsudaira T, Yoshikawa E, Ando I, Futatsubashi M, Tsukada H, Ouchi Y
    • Journal Title

      Neurology

      Volume: in press Issue: 15 Pages: 1592-1604

    • DOI

      10.1212/wnl.0000000000009249

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coexistence of cerebral hypometabolism and neuroinflammation in the thalamo-limbic-brainstem region in young women with functional somatic syndrome2020

    • Author(s)
      Matsudaira T, Terada T, Obi T, Yokokura M, Takahashi Y, Ouchi Y.
    • Journal Title

      EJNMMI Res.

      Volume: 10(1) Issue: 1 Pages: 29-29

    • DOI

      10.1186/s13550-020-00617-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study2020

    • Author(s)
      Yokokura Masamichi、Takebasashi Kiyokazu、Takao Akiyo、Nakaizumi Kyoko、Yoshikawa Etsuji、Futatsubashi Masami、Suzuki Katsuaki、Nakamura Kazuhiko、Yamasue Hidenori、Ouchi Yasuomi
    • Journal Title

      Molecular Psychiatry

      Volume: - Issue: 9 Pages: 12-12

    • DOI

      10.1038/s41380-020-0784-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neural correlates of standing imagery and execution in Parkinsonian patients: the relevance to striatal dopamine dysfunction2020

    • Author(s)
      Mori Y, Yoshikawa E, Futatsubashi M, Ouchi Y
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 10 Pages: e0240998-e0240998

    • DOI

      10.1371/journal.pone.0240998

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neural correlates of head restraint: unsolicited neuronal activation and dopamine release2020

    • Author(s)
      Inubushi T, Ito M, Mori Y, Futatsubashi M, Sato K, Ito S, Yokokura M, Shinke T, Kameno Y, Kakimoto A, Kanno T, Okada H, Ouchi Y, Yoshikawa E.
    • Journal Title

      Neuroimage

      Volume: 224 Pages: 117434-117434

    • DOI

      10.1016/j.neuroimage.2020.117434

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] A reverse translational study on dementia using MC-I PET imaging, extending to the current biomarker study2023

    • Author(s)
      Yasuomi Ouchi
    • Organizer
      第2回Hamamatsu -MCSA Meeting
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PET imaging for brain homeostasis in reverse translational studies on dementia2023

    • Author(s)
      Yasuomi Ouchi
    • Organizer
      19回International conference: Peace through Mind/Brain Science
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アルツハイマー病のPET画像診断2022

    • Author(s)
      尾内康臣
    • Organizer
      第63回日本神経学会総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease: PET study2021

    • Author(s)
      Tatsuhiro Terada, Joseph Therriault, Min Su Peter Kang, Takashi Matsudaira, Tomoyasu Bunai, Tomokazu Obi, Hirotsugu Takashima, Norihiko Kawaguchi, Yasukiyo Araki, Hideo Tsukada, Pedro Rosa-Neto, Yasuomi Ouchi
    • Organizer
      第62回 日本神経学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] PETを用いたアルツハイマー病のミトコンドリア障害と神経変性との病態関連研究2021

    • Author(s)
      寺田達弘、横倉正倫、武内智康、松平敬史、小尾智一、塚田秀夫、尾内康臣
    • Organizer
      第24回 ヒト脳機能マッピング研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Transcranial direct-current stimulation enhances dopamine release and attentiveness2020

    • Author(s)
      Yasuomi Ouchi, Tomoyasu Bunai, Toru Hirosawa, Mina Fukai, Shigeru Ito, Etsuji Yoshikawa, Mitsuru Kikuchi.
    • Organizer
      26回Annual Meeting of the Organization for Human Brain Mapping
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 認知症診療に繋げる分子イメージングの成果と展望2020

    • Author(s)
      尾内康臣
    • Organizer
      第39回日本認知症学会
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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