| Project/Area Number |
26461376
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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 |
Endocrinology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Hashimoto Koshi 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (30396642)
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| Co-Investigator(Renkei-kenkyūsha) |
OGAWA Yoshihiro 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70291424)
KAMEI Yasutomi 京都府立大学, 生命環境科学研究科, 教授 (70300829)
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| Research Collaborator |
KAWAHORI Kenichi
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 甲状腺機能低下 / 妊娠期 / BDNF / 海馬 / 学習・認知能力低下 / 水迷路試験 / DNAメチル化 / DOHaD / 甲状腺ホルモン / 妊娠 / 母体甲状腺機能低下症 / 行動試験 / 中枢神経系 / エピゲノム記憶 / 甲状腺機能低下症 / エピジェネティクス / 高次脳機能 |
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| Outline of Final Research Achievements |
Experimental rodents have shown that maternal hypothyroxinemia during pregnancy may adversely affect neurodevelopment in offspring, resulting in irreversible cognitive deficits. This could be due to persistent reduced expression of hippocampal brain derived neurotrophic factor gene (Bdnf), which plays a crucial role in the central nervous system (CNS) development. However, the underlying molecular mechanism remains unclear. In the current study, we showed that mild maternal hypothyroxinemia during pregnancy induced impaired learning capacity of mouse offspring in adulthood. We also demonstrated that prolonged reduction in hippocampal Bdnf expression of the offspring in according to persistent DNA hypermethylation in the promoter region of Bdnf exon Ⅳ. Thus, we provide the first evidence that mild maternal hypothyroixinemia induces persistent DNA hypermethylation in Bdnf in the offspring, which could confer long-term cognitive disorder.
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