Microglial contribution on higher order of brain function and their pathology
Project/Area Number |
18H02598
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 48020:Physiology-related
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Research Institution | Nagoya University (2020) Kobe University (2018-2019) |
Principal Investigator |
WAKE Hiroaki 名古屋大学, 医学系研究科, 教授 (90455220)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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Keywords | ミクログリア / 血液脳関門 / シナプス / 学習 / 免疫 |
Outline of Final Research Achievements |
In this study, we focused on microglia and aimed to elucidate psychiatric pathology from their physiological functions on synapses and blood vessels. Using in vivo imaging, we found that microglia migrate into cerebral blood vessels during systemic inflammation and contribute to the permeability of the blood-brain barrier in a time-specific manner by altering the expression of tight junction-related factors and phagocytic factors. In addition, we found that microglia modulate their synaptic effects by regulating their projection dynamics during higher brain functions (motor learning). These synaptic modulation mechanisms are dependent on the sensory input in the sensory cortex, suggesting a role for microglia in heterogeneous sensory plasticity.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果によって、ミクログリアを標的とした中枢神経系疾患に対する新たな創薬の可能性を創出することができた。さらにミクログリアによるシナプス可塑性を制御することで、中枢神経系疾患の回復期に介入する可能性も考えられる。さらに異種感覚の可塑性のミクログリアによる制御の解明は学術的にも非常に意義深い。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Pain induces stable, active microcircuits in the somatosensory cortex that provide a new therapeutic target.2021
Author(s)
Okada T, Kato D, Nomura Y, Obata N, Quan X, Morinaga A, Yano H, Guo Z, Aoyama Y, Tachibana Y, Moorhouse AJ, Matoba O, Takiguchi T, Mizobuchi S and Wake H
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Journal Title
Sci Adv
Volume: 7
Issue: 12
Pages: 8261-8261
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Maternal Immune activation induces sustained changes in fetal microglia motility2020
Author(s)
Ozaki K, Kato D, Ikegami A, Hashimoto A, Sugio S, Guo Z, Shibushita M, Tatematsu T, Haruwaka K, Moorhouse AJ, Yamada H, Wake H
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Journal Title
Sci Rep
Volume: 10
Issue: 1
Pages: 21378-21378
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Negative feedback control of neuronal activity by microglia.2020
Author(s)
Badimon A, Strasburger HJ, Ayata P, Chen X, Nair A, Ikegami A, Hwang P, Chan AT, Graves SM, Uweru JO, Ledderose C, Kutlu MG, Wheeler MA, Kahan A, Ishikawa M, Wang YC, Loh YE, Jiang JX, Surmeier DJ, Robson SC, Junger WG, Sebra R, Calipari ES, Kenny PJ, Eyo UB, Colonna M, Quintana FJ, Wake H, Gradinaru V, Schaefer A.
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Journal Title
Nature
Volume: 586
Issue: 7829
Pages: 417-423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Microglia Enhance Synapse Activity to Promote Local Network Synchronization2018
Author(s)
Ryohei Akiyoshi, Hiroaki Wake, Daisuke Kato, Hiroshi Horiuchi, Riho Ono, Ako Ikegami, Koichiro Haruwaka, Toshiaki Omori, Yoshihisa Tachibana, Andrew Moorhouse, Junichi Nabekura
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Journal Title
eNeuro
Volume: 5
Issue: 5
Pages: 0088-18
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Regulation of myelin structure and conduction velocity by perinodal astrocytes.2018
Author(s)
3.Dutta D, Woo DH, Lee PR, Pajevic S, Bukalo O, Huffman WC, Wake H, Basser PJ, Sheikhbahaei S, Lazarevic V, Smith JC & Fields RD.
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Journal Title
Proc Natl Acad Sci USA
Volume: Nov 13;115(46)
Pages: 11832-11837
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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