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Elucidation of the multifunctional signaling of estrogen using the visualization of estrogen responsible neurons

利用负责雌激素的神经元的可视化阐明雌激素的多功能信号传导

基本信息

批准号：
17500215
负责人：
HAMADA Tomohiro
金额：
$ 2.37万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Estrogen plays an essential role for reproduction, plasticity and neuroprotection to affect on the central nervous system. The purpose of the present study is to examine the mechanisms of estrogen action using the visualized neurons that are responsible to estrogen in the estrogen receptor gene promoter transgenic rats. Most important result is that EGFP expression under the control of estrogen receptor gene promoter is a specific marker for the sexually dimorphic nucleus of the preoptic area. Because sexual dimorphism of this nucleus is established by estrogen during the perinatal period, the new, live marker would contribute to clarify the molecular mechanisms of the sexual differentiation. On the other hand, EGFP expression is observed in the hippocampus that is noted function of estrogen for the plasticity and neurogenesis. We determined acute and chronic effects of physiological concentration of estrogen on the outward potassium currents in the primary cultured EGFP hippocampal neurons. Immature neurons showed the facilitated effect of 48 h treatment of estrogen, however, mature neurons exhibited the suppressive effect on the outward potassium currents. After the 48 h treatment of estrogen, bath application of 250 pM estrogen enhanced the potassium currents. These results suggest that estrogen influence the development and excitability of hippocampal neurons. One more thing to be noted is that there is the sex difference in the number of EGFP expressed cells in the area postrema and the nucleus tractus solitarius that are known to play an important role for cardiovascular regulation. Because hypertension is inhibited by estrogen in female, we could expect to clear the mechanisms of estrogen function on the cardiovascular regulation. Thus, we can show a number of the important results and we would like to study further to make clear the molecular mechanisms of estrogen function in the central nervous system.

雌激素对中枢神经系统的生殖、可塑性和神经保护起着至关重要的作用。本研究的目的是利用雌激素受体基因启动子转基因大鼠中负责雌激素的可视化神经元来研究雌激素的作用机制。最重要的结果是雌激素受体基因启动子控制下的EGFP表达是视前区两性二态核的特异性标记。由于该细胞核的性别二态性是在围产期由雌激素建立的，新的活标记将有助于阐明性别分化的分子机制。另一方面，在海马中观察到EGFP的表达，这是雌激素在可塑性和神经发生中的作用。我们测定了雌激素生理浓度对原代培养的EGFP海马神经元外向钾电流的急性和慢性影响。未成熟神经元在雌激素处理48 h后表现出促进作用，而成熟神经元对外向钾电流表现出抑制作用。雌激素处理48 h后，浴敷250 pM雌激素可增强钾电流。这些结果表明雌激素影响海马神经元的发育和兴奋性。还有一点需要注意的是，在后脑区和孤束核中EGFP表达细胞的数量存在性别差异，这些细胞在心血管调节中起着重要作用。由于雌性激素对女性高血压有抑制作用，我们有望明确雌性激素在心血管调节中的作用机制。因此，我们可以展示一些重要的结果，我们愿意进一步研究，以明确雌激素在中枢神经系统中的功能的分子机制。