| Project/Area Number |
20700292
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neuroscience in general
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
MATSUDA Ken ichi Kyoto Prefectural University of Medicine, 医学研究科, 准教授 (40315932)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 性差 / 性行動 / エピジェネティックス / エストロゲン / アンドロゲン / 性分化 / ヒストン / エピジェネティクス / アセチル化 |
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| Research Abstract |
Epigenetic histone modifications are emerging as potentially important mechanisms to convey effect of hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. We found that histones associated with the estrogen receptor alpha and aromatase gene promoters in the medial preoptic area were differentially acetylated between the sexes at embryonic day 21, and this difference in acetylation state was rearranged by postnatal day 3. Moreover, histone deacetylase (HDAC) 2 and 4 bound to ERalpha and aromatase promoters at higher frequencies in males than in females. We inhibited HDACs in vivo by intracerebroventricular infusion of the HDAC inhibitor, trichostatin A (TSA), or antisense oligodeoxynucleotide (ODN) directed against the mRNAs for HDAC2 and 4 in newborn male rats, and examined the effects on masculinization of the brain by analyzing male sexual behavior in adulthood. Male sexual behaviors were reduced by either administrations of TSA or antisense ODN during the neonatal period. These results demonstrate that histone deacetylase activity during the early postnatal period plays a crucial role in the masculinization of the brain through sexual dimorphic modifications of histone acetylation status.
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