Analysis of involvement of epigenetics in the sexual differentiation of the brain
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 |
Research Field |
Neuroscience in general
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Research Institution | Kyoto Prefectural University of Medicine |
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 |
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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Report
(3 results)
Research Products
(81 results)
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[Journal Article] Characteristics of donor and host cell in the early remodeling process after transplant of Achilles tendon with and without live cells for the treatment of rotator cuff defect.2010
Author(s)
Tachiiri H, Morihara T, Iwata Y, Yoshida A, Kajikawa Y, Kida Y, Matsuda KI, Fujiwara H, Kurokawa M, Kawata M, Kubo T.
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Journal Title
Journal of Shoulder and Elbow Surgery (in press)
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Peer Reviewed
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[Journal Article] Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs.2009
Author(s)
Sawamura K, Ikeda T, Nagae M, Okamoto SI, Mikami Y, Ikoma K, Yamada T, Sakamoto H, Matsuda KI, Tabata Y, Kawata M, Kubo T.
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Journal Title
Tissue Engineering 15
Pages: 3719-3727
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Peer Reviewed
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[Journal Article] Behavior of host and graft cells in the early remodeling process of rotator cuff tendon defect in a transgenic animal model.2008
Author(s)
Iwata Y, Morihara T, Tachiiri H, Kajikawa Y, Yoshida A, Tokunaga D, Matsuda KI, Sakamoto H, Kurokawa M, Kawata M, Kubo T.
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Journal Title
Journal of Shoulder and Elbow Surgery 17
Pages: 101-107
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Peer Reviewed
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[Presentation] 多血小板血漿を用いた椎間板変性に関するMRI・組織細胞化学研究2009
Author(s)
澤村和秀, 池田巧, 長江将輝, 三上靖夫, 長谷斉, 岡本慎一, 生駒和也, 山田哲也, 松田賢一, 田端康彦, 河田光博, 久保俊一
Organizer
第50回日本組織細胞化学会
Place of Presentation
大津
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