| Project/Area Number |
17K07114
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Nagoya City University |
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Principal Investigator |
KANEKO NAOKO 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (20464571)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 神経科学 / 再生医学 / ニューロン新生 / 脳梗塞 |
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| Outline of Final Research Achievements |
New neurons are continuously generated in the ventricular-subventricular zone in the postnatal mammalian brain. The newly generated immature neurons (neuroblasts) are highly motile and migrate toward the injured area. However, the ability of the mammalian brain to regenerate neuronal circuits is quite limited. Here, we investigated the mechanisms of neuronal regeneration using a mouse model for ischemic stroke. Immediately after stroke, astrocytes are activated with a larger soma and thicker processes. The neuroblasts used Slit1 to disrupt the actin cytoskeleton in activated astrocytes for their migration. By Slit1 overexpression, the transplanted neuroblasts could migrate closer to the lesion. Some of them matured and integrated into the neuronal circuit. Furthermore, Slit1 overexpression in neuroblasts induced functional recovery over 10 weeks. Taken together, manipulation of neuroblast migration is critical for functional regeneration in cell-based therapies for brain injury.
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| Academic Significance and Societal Importance of the Research Achievements |
脳梗塞後の脳では顕著なアストロサイトの活性化が生じる。本研究では、これまでほとんど分かっていなかった活性化アストロサイトと新生ニューロンの相互作用メカニズムの一端を明らかにして、その操作により新生ニューロンの傷害部への移動を促進することに成功した。また、このメカニズムを応用して新生ニューロンの移動を操作することによって、最終的な分布位置、回路形成や機能再生の効率も変化することを明らかにして、脳の再生過程における新生ニューロンの分布制御の重要性を提示した。これらは、細胞を用いて傷害脳を再生する新たな治療戦略の確立にも有用な知見である。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach a lesion for functional regeneration.2018
Author(s)
Kaneko N, Herranz-Perez V, Otsuka T, Sano H, Ohno N, Omata T, Nguyen HB, Thai TQ, Nambu A, Kawaguchi Y, Garcia-Verdugo JM, Sawamoto K.
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Journal Title
Science Advances
Volume: 4
Issue: 12
Pages: 0618-0618
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Detachment of Chain-Forming Neuroblasts by Fyn-Mediated Control of cell-cell Adhesion in the Postnatal Brain.2018
Author(s)
Fujikake K, Sawada M, Hikita T, Seto Y, Kaneko N, Herranz-Perez V, Dohi N, Homma N, Osaga S, Yanagawa Y, Akaike T, Garcia-Verdugo JM, Hattori M, Sobue K, Sawamoto K.
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Journal Title
Journal of Neuroscience
Volume: 38
Issue: 19
Pages: 4598-4609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Radial glial fibers support neuronal migration and regeneration after neonatal brain injury.2018
Author(s)
Jinnou H, Sawada M, Kawase K, Kaneko N, Herranz-Perez V, Miyamoto T, Kawaue T, Miyata T, Tabata Y, Akaike T, Garcia-Verdugo JM, Ajioka I, Saitoh S, Sawamoto K.
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Journal Title
Cell Stem Cell
Volume: 22
Issue: 1
Pages: 128-137
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] New neurons migrate through the glial meshwork using Slit1 to approach the lesion for functional recovery.2019
Author(s)
N. Kaneko, V. Herranz-Perez, T. Otsuka, H. Sano, N. Ohno, T. Omata, H. B. Nguyen, T. Q. Thai, A. Nambu, Y. Kawaguchi, J. M. Garcia-Verdugo, K. Sawamoto.
Organizer
Neuroscience 2019 (Society for Neuroscience)
Related Report
Int'l Joint Research
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[Presentation] New neurons reach and regenerate stroke-injured brain tissue by clearing a path through glia.2019
Author(s)
N. Kaneko, V. Herranz-Perez, T. Otsuka, H. Sano, N. Ohno, T. Omata, H. B. Nguyen, T. Q. Thai, A. Nambu, Y. Kawaguchi, J. M. Garcia-Verdugo, K. Sawamoto.
Organizer
International Society for Neurochemistry- American Society for Neurochemistry Meeting
Related Report
Int'l Joint Research
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[Presentation] Enhanced neuronal migration through activated glia promotes post-stroke neuronal regeneration2019
Author(s)
N. Kaneko, V. Herranz-Perez, T. Otsuka, H. Sano, N. Ohno, T. Omata, H.B. Nguyen, T.Q. Thai, A. Nambu, Y. Kawaguchi, J.M. Garcia-Verdugo, K. Sawamoto
Organizer
The 9th Federation of the Asian and Oceanian Physiological Societies Congress
Related Report
Int'l Joint Research
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