Analysis of involvement of epigenetics in the sexual differentiation of the brain

表观遗传学参与大脑性别分化的分析

• 批准号: 20700292
• 负责人: MATSUDA Ken ichi
• 金额: $ 2.83万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20700292/
• 关键词: 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

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.

表观遗传组蛋白修饰正在成为将激素环境的影响传递到发育中的大脑的潜在重要机制。我们假设性类固醇激素在发育早期改变组蛋白乙酰化状态对大脑的性别分化很重要。我们发现，组蛋白与雌激素受体α和芳香化酶基因启动子在内侧视前区的性别之间的差异乙酰化在胚胎的第21天，这种差异乙酰化状态被重新排列的出生后第3天。此外，组蛋白去乙酰化酶（HDAC）2和4结合ER α和芳香化酶启动子在男性中的频率高于女性。我们通过脑室内输注HDAC抑制剂、阿司他丁A（TSA）或针对新生雄性大鼠HDAC 2和4 mRNA的反义寡脱氧核苷酸（ODN）来抑制体内HDAC，并通过分析成年期雄性性行为来检查对大脑男性化的影响。在新生儿期，TSA或反义ODN均可降低雄性大鼠的性行为。这些结果表明，组蛋白去乙酰化酶活性在出生后早期起着至关重要的作用，在大脑的雄性化，通过性二态性修改组蛋白乙酰化状态。

项目成果

Sexual Differentiation of Preoptic Area and Hypothalamic Nuclei in Rat

大鼠视前区和下丘脑核团的性别分化

• 发表时间: 2008
• 作者: Takanami K;Sakamoto H;Matsuda KI;Hosokawa K;Nishi M;Prossnitz ER;Kawata M.;Ken-Ichi Matsuda
• 通讯作者: Ken-Ichi Matsuda

Characterisctics of donor and host cells in the early remodeling process after trans-plant of tendon with and without live cells for the treatment of rotator cuff defect.

移植有和没有活细胞的肌腱治疗肩袖缺损后早期重塑过程中供体和宿主细胞的特征。

• 发表时间: 2010
• 期刊: Journal of Shoulder Elbow Surgery (印刷中)
• 作者: 西垣泰宏;寺前順之介;深井朋樹;Hisakazu Tachiiri
• 通讯作者: Hisakazu Tachiiri

Behavior of host and graft cells in the early remodeling process of rotator cuff tendon defect in a transgenic animal model.

转基因动物模型中肩袖肌腱缺损早期重塑过程中宿主细胞和移植细胞的行为。

• 发表时间: 2008
• 期刊: Journal of Shoulder and Elbow Surgery 17
• 作者: Iwata Y;Morihara T;Tachiiri H;Kajikawa Y;Yoshida A;Tokunaga D;Matsuda KI;Sakamoto H;Kurokawa M;Kawata M;Kubo T.
• 通讯作者: Kubo T.

GFPキメララットを用いた椎間板の変性過程における骨髄由来細胞の動態解析

GFP嵌合大鼠椎间盘退变过程中骨髓来源细胞的动态分析

• 发表时间: 2009
• 作者: 橋本隆;松田賢一;河田光博;橋本隆;高浪景子;澤村和秀;澤村和秀
• 通讯作者: 澤村和秀

脱髄変性ラットにおける膜型エストロゲン受容体GPR30を介した再ミエリン化促進作用

通过膜雌激素受体 GPR30 促进脱髓鞘大鼠的髓鞘再生

• 发表时间: 2009
• 作者: 橋本隆;松田賢一;河田光博;橋本隆;高浪景子;澤村和秀;澤村和秀;森浩子;平原幸恵
• 通讯作者: 平原幸恵