| Project/Area Number |
26670512
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
Fukuda Atsuo 浜松医科大学, 医学部, 教授 (50254272)
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| Co-Investigator(Renkei-kenkyūsha) |
AKITA Tenpei 浜松医科大学, 医学部, 准教授 (00522202)
WATANABE Miho 浜松医科大学, 医学部, 助教 (10399321)
MUTOH Hiroki 浜松医科大学, 医学部, 助教 (60443040)
HATA Kenichiro 国立成育医療研究センター, 周産期病態研究部, 部長 (60360335)
UCHIDA Shinichi 東京医科歯科大学, 医歯学総合研究科, 教授 (50262184)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | ストレス / 脳発達 / WNK / KCC2 / GABA / コルチコステロン / GAD / 低栄養 / 塩分負荷 / CRH |
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| Outline of Final Research Achievements |
We have developed maternal undernutrition model, in which interaction with fetal GAD67 deficiency (GAD67+/GFP) was observed. That was, in contrast to dams, ACTH and CORT increments were significant in heterozygotes. Since WNK3 kinases is an essential element in the signaling cascade regulating Cl－ concentrations after salt intake, we have used a WNK3 KO mice and examined membrane properties. Loss of WNK3 activity significantly reduced neuronal excitability, as evidenced by hyperpolarized resting membrane potential, decreases in input resistance and membrane time constant, and a resulting increase in the threshold current for action potential generation. We examined GAD67+/GFP pups underwent prenatal stress, which showed impaired neurogenesis of parvalbumin-positive GABAergic neurons as well as behavioral abnormality. We found multiple genes related to neurogenesis and/or neural migration were either hyper-methylated or hypo-methylated in GAD67+/GFP underwent prenatal stress.
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