| Project/Area Number |
18K07802
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Jikei University School of Medicine |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 発達性てんかん性脳症 / SCN1A / モデルラット / 磁気共鳴画像 / てんかん発作 / 脳神経活動 / ガンマアミノ酪酸 / 疾患モデルラット / 小動物MRI / 難治てんかん / 脳波 / 移植・再生医療 |
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| Outline of Final Research Achievements |
Dravet syndrome is an infantile-onset developmental and epileptic encephalopathy. Impaired inhibition in the brain neuronal networks has been reported to be the main mechanism of this syndrome. The aim of this research is to elucidate developmental alteration in the regional brain activities of a rat model for Dravet syndrome, initially intending to elucidate target brain regions for future development of cell transplantation therapy. Manganese-enhanced magnetic resonance imaging technique was employed to quantitatively evaluate the activities in rats at various developmental stages. As a result, a significant increase in the basal activities occurred during the third postnatal week in the widespread brain areas. The transient hyperactivity could be relieved by administration of bumetanide, an NKCC1 inhibitor, indicating that a delay in inhibitory network maturation may be involved in this phenomenon.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでにドラベ症候群の主な原因や病態機序に関する報告はあるが、成長とともにダイナミックに変化する臨床症状に対応する細胞分子ネットワーク病態の詳細は明らかとなっていなかった。本研究で疾患脳の大脳活動性変化をin vivoで、経齢的に、全脳レベルで、解剖学的に、明らかにできたことはこれまでにない成果である。さらに、マンガン造影磁気共鳴画像法のてんかん研究における可能性を示したことも重要である。これらは今後の病態理解、ならびに年齢や症状に応じたより適切な治療開発を目指す研究において役立ち、将来的には本症をもつ人々の福音となることが期待される。
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