GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance.
GPR30 is positioned to mediate estrogen effects on basal forebrain cholinergic neurons and cognitive performance.
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DOI：
10.1016/j.brainres.2010.11.098
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发表时间：
2011-03-16
期刊：
影响因子：
2.9
通讯作者：
Gibbs RB
中科院分区：
文献类型：
--
作者：
Hammond R;Gibbs RB
雌激素治疗对认知能力的有益作用随着年龄和卵巢功能丧失后的时间而减少。这导致了“机会之窗”假说，该假说指出，雌激素治疗必须在绝经后的有限时间内进行，才能有效。雌激素治疗对认知能力的影响至少部分是由于对支配海马和皮质的胆碱能传入神经的影响，并且已经表明，随着年龄和绝经后时间的增加，雌激素效应的丧失是由于这些投射功能的实质性降低。这些影响背后的机制尚不清楚。GPR30是一种新的G蛋白偶联雌激素受体，在脑和其他组织中表达。我们最近的研究表明，GPR30在大脑中对空间学习、记忆和注意力很重要的区域表达。此外，GPR30在基底前脑中的绝大多数胆碱能神经元中表达，并且似乎是基底前脑胆碱能功能的重要调节剂。我们假设GPR30在介导雌二醇对基底前脑胆碱能神经元的直接作用中起着重要作用，并对认知能力产生相应的影响。因此，GPR30可能是开发新疗法的重要靶点，可以增强或恢复雌激素对老年女性认知能力的影响。在这里，我们简要回顾了胆碱能假说，并总结了我们的研究结果，迄今显示的影响，GPR30激动剂和拮抗剂对基底前脑胆碱能功能和认知能力。
Beneficial effects of estrogen therapy on cognitive performance diminish with age and time following the loss of ovarian function. This has led to the ‘Window of Opportunity’ hypothesis, which states that estrogen therapy must be administered within a limited period of time following menopause in order to be effective. Effects of estrogen therapy on cognitive performance are due, at least in part, to effects on cholinergic afferents innervating the hippocampus and cortex, and it has been suggested that the loss of estrogen effect with age and time following menopause is due to a substantial reduction in the function of these projections. The mechanisms that underlie the effects are not clear. GPR30 is a novel G-protein coupled estrogen receptor that is expressed in brain and other tissues. Our recent studies show that GPR30 is expressed in areas of the brain important for spatial learning, memory, and attention. In addition, GPR30 in expressed by the vast majority of cholinergic neurons in the basal forebrain, and appears to be an important regulator of basal forebrain cholinergic function. We hypothesize that GPR30 plays an important role in mediating direct effects of estradiol on basal forebrain cholinergic neurons, with corresponding effects on cognitive performance. Hence, GPR30 may be an important target for developing new therapies that can enhance or restore estrogen effects on cognitive performance in older women. Here we briefly review the cholinergic hypothesis and summarize our findings to date showing effects of a GPR30 agonist and antagonist on basal forebrain cholinergic function and cognitive performance.
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影响因子：
56.9
作者：
DEUTSCH, JA
通讯作者：
DEUTSCH, JA
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作者：
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作者：
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