| Project/Area Number |
17H04247
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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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| Research Field |
Psychiatric science
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| Research Institution | Hamamatsu University School of Medicine |
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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)
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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, 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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| Keywords | アルツハイマー病 / 脳神経画像 / 脳・神経 |
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| 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
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| 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。
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