| Project/Area Number |
18K06510
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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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| Review Section |
Basic Section 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Nihon University |
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Principal Investigator |
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | RNA-seq / 神経血管ユニット / 毛細血管密度 / CGRP / Runx1 / RNA-seq解析 / ミクログリア / 筋萎縮性側索硬化症 / 次世代シークエンス / 神経変性疾患 |
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| Outline of Final Research Achievements |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective degeneration of motor neurons. Although the major hallmark of ALS is the motor phenotype, alterations of non-neuronal cells were also reported in ALS model mice. However, the role of non-neuronal cell impairment for axonal degeneration in pre-symptomatic ALS is still unknown. To identify which cell types were more likely to be affected by the ALS pathogenesis, we analyzed differentially expressed genes (DEGs) with known cell-type markers. The changes of putative microglia, meningeal cells / Schwann cells, and oligodendrocyte precursor cells were identified as particular abnormalities in the ALS spinal cord at postnatal day 30 (denervated neuromuscular junction). In addition, alterations in the vasculature existed prior to neuromuscular junction denervation. These results suggest that various cell types contribute to axonal degeneration in pre-symptomatic ALS.
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| Academic Significance and Societal Importance of the Research Achievements |
ALSの進行を抑制する因子についてはこれまでに多くの報告がある。しかしながら、発症を遅らせる因子の報告はほとんどない。発症前の軸索変性に関わる分子メカニズムが解明できれば、発症を遅らせる研究への適用が可能であり、その意義は大きい。また、ALSの初期病変に関わる因子は、患者の発症前診断・早期治療につながる情報を得られるだけでなく、運動ニューロンの軸索変性を伴うサルコペニア（加齢に伴う筋減少）のような他疾患への応用・発展も期待される。
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