| Project/Area Number |
22K15707
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Li Jiayi 名古屋大学, 医学系研究科, 研究員 (40867420)
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| Project Period (FY) |
2022-02-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | TDP-43 / ALS / synapse / neuron / ニューロン / シナプス / ミクログリア / FTLD |
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| Outline of Research at the Start |
In our preliminary research, synaptic loss was observed in the brain of neuro-specific TDP-43 knockout (TDP-43cKO) mouse without either neuronal loss nor axonal degeneration. Transcriptome analyses showed that the expressions of various genes potentially regulating synapse plasticity and related to neuron-glia interaction were changed in TDP-43cKO neuron.
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| Outline of Final Research Achievements |
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, which affects both upper and lower motor neuron. Synaptic damage is observed in the early events, followed by neurodegeneration in ALS/FTLD. This study investigates the role of TDP-43 in synapse dysfunction during ALS progression. We created mice with conditional knockout of TDP-43 in neurons (TDP-43cKO). These mice exhibited reduced synapse numbers without obvious neuronal death and axonal damage. We isolated control and TDP-43 knockout neurons and analyzed their gene expression (RNAseq). This analysis revealed changes in genes associated with synapse function. Additionally, TDP-43cKO mice displayed memory deficits in novel object recognition test.
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| Academic Significance and Societal Importance of the Research Achievements |
ALS/FTLDでは、シナプス損傷が特徴的な病理学的変化である一方、神経細胞におけるTDP-43タンパク質とシナプス可塑性との関係は依然として不明である。我々の研究では、TDP-43タンパク質の喪失がマウスにおいてシナプス喪失と機能障害を引き起こすことを明らかにした。この発見は、ALS治療への新たな可能性を示唆している。
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