| Project/Area Number |
16K08470
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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 |
General anatomy (including histology/embryology)
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| Research Institution | Kumamoto University |
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Principal Investigator |
ESUMI Shigeyuki 熊本大学, 大学院生命科学研究部(医), 講師 (90404334)
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| Co-Investigator(Kenkyū-buntansha) |
浜崎 禎 熊本大学, 大学院生命科学研究部(医), 准教授 (60433033)
西村 方孝 熊本大学, 大学院生命科学研究部(医), 助教 (80613398)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 視床下部 / 神経発生 / GABA / 抑制性神経 / GABAニューロン / 臨界期 / 摂食行動 / 摂食障害 / 発生 / 発達 / VGAT / Nkx2-1 / 摂食中枢 / GABAergic Neuron / 神経回路形成 / 摂食 / 補償機構 / 細胞系譜 / cre / 神経科学 / 発生・分化 |
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| Outline of Final Research Achievements |
It has never known that eating behaviors under stress that derived from genetic factors. GABA is a major inhibitory neurotransmitter in mammalian nervous system. Recently, it has been reported that GABA influence to progenitor proliferation and migration and synaptogenesis during development. Here, to assess the functions of GABA in hypothalamic development, we utilized Nkx2-1-cre VGAT floxed mice that can delete GABA secretion partially. As the result, the mice die until P2 without cleft palate and omphalocele. These data suggest that GABA is important for CNS development and survival in neonatal mice. Further, to investigate molecular mechanisms underline the CNS dysfunction, we performed RNA-seq approach. As it turns out, more than 250 differentially expressed genes were identified. Interestingly, the gene ontology terms associated with these genes include "neuron development" and "axon guidance" groups. Further studies are required to support RNA-seq analysis in future.
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| Academic Significance and Societal Importance of the Research Achievements |
拒食症及び過食症の総称である摂食障害は心理的ストレスや環境的要因、遺伝的背景などの複合的な要素により生じる。中枢を原因とする摂食障害は一卵性双生児の発症一致率が高いことや家族集積性の研究から遺伝的な関与が示唆されているが、その発症メカニズムは明らかになっていない。申請者は遺伝子改変マウスを用いて研究を進め、成体では神経伝達物質として働くGABA（γアミノ酪酸）が、視床下部や大脳皮質の発生発達に重要な役割を果たしていることを明らかにした。
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