| Project/Area Number |
18390070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Nippon Medical School |
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Principal Investigator |
SAKUMA Yasuo Nippon Medical School, 大学院・医学研究科, 教授 (70094307)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Masakatsu 日本医科大学, 医学部, 准教授 (90143239)
KIYAMA Yuko 日本医科大学, 医学部, 講師 (60234390)
KONDO Yasuhiko 日本医科大学, 医学部, 講師 (00192584)
ORIKASA Chitose 日本医科大学, 医学部, 助教 (20270671)
HAMADA Tomohiro 日本医科大学, 医学部, 助教 (90312058)
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| Project Period (FY) |
2006 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥17,450,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2007: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | 性分化 / 脳の性差 / エストロゲン / 細胞移動 / 細胞新生 / アポトーシス / エストロゲン受容体 / 蛍光タンパク / 性腺刺激ホルモン放出ホルモン(GnRH) / γアミノ酪酸(GABA) / 電位依存性カルシウムチャネル(VGCC) / カリウムチャネル / 環境 / 生理学 / 性ホルモン / 細胞死 / チャネル / 行動生理学 / 神経内分泌学 / 生殖内分泌学 / ラットGnRHニューロン / 蛍光タンパク遺伝子 / GABA_A受容体 / サブユニット / ニューロステロイド / メラトニン / MT1受容体 / 性差 / 蛍光タンパク遣伝子 / 芳香化 / SDN-POA / AVPV / GnRH / GABA / NKCC1 |
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| Research Abstract |
In the rat, estrogen determines sexual phenotype of the brain, acting at a critical period as neonates. The sexual phenotype thus established persists into adulthood, both in morphology and electrophysiology. In the adults, the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is larger in males than in females. The anteroventral periventricular nucleus (AVPV) is packed with estrogen receptor (ER) ss-positive neurons in females but these cells scatter in the more lateral areas in males. Estrogen regulates axonal excitability of projection neurons in the ventromedial hypothalamus and those in the preoptic area in diametrically opposite directions in females but not in males. Male phenotype depends on the presence of estrogen as neonates ; the lack leads to the female phenotype. This research project focused intracellular signal cascades, which are kindled by estrogen through estrogen receptor (ER) α and culminate in neurogenesis, migration or cell death. 1) By using 5'-RACE we identified a new leader exon and untranslated internal exons in ERα gene. These exons were used for site-specific transcription of ERα ; 2) In a trait of transgenic rat, which express EGFP under the control of ERα promoter 0/B, ERα-positive neurons in the SDN-POA, but not those in the adjacent areas, were fluorescent. Time lapse movies showed the establishment of the SDN-POA as a result of neuronal migration ; 3) In another trait of transgenic rat, in which gonadotropin-releasing hormone (GnRH) neurons were tagged by EGFP, activation of GABAA_A receptors depolarized adult GnRH neurons due to their high chloride ion content ; 4) DNA microarray, PCR and Western-blot analysis demonstrated site-specific, opposite regulations of apoptosis- and migration-related genes in the SDN-POA and AVPV.
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