Multi-layer illustration of neuronal viability and microglial polarization in Alzheimer's disease
| Project/Area Number |
20H03600
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Hamamatsu University School of Medicine |
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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)
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| 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)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| 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)
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| Keywords | アルツハイマー病 |
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| 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。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(26 results)
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[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
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Journal Title
EMBO Molecular Medicine
Volume: -
Issue: 5
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Mol Psychiatry
Volume: -
Issue: 4
Pages: 2106-2113
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Mol Neurodegener
Volume: 16
Issue: 1
Pages: 28-28
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Neuroimage
Volume: 224
Pages: 117434-117434
DOI
Related Report
Peer Reviewed
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[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
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