Role of GPR30 in mediating estradiol effects on acetylcholine release in the hippocampus.
Role of GPR30 in mediating estradiol effects on acetylcholine release in the hippocampus.
复制标题
GPR30在介导雌二醇对海马乙酰胆碱释放的作用中的作用。
DOI：
10.1016/j.yhbeh.2014.06.002
复制
发表时间：
2014-07
影响因子：
3.5
通讯作者：
Hammond, R.
中科院分区：
文献类型：
--
作者：
Gibbs, R. B.;Nelson, D.;Hammond, R.
关键词：
我们假设雌二醇至少部分通过激活新型雌激素受体GPR 30来增强基底前脑胆碱能功能和认知能力。在此，我们评价了雌二醇、G-1（一种选择性GPR 30激动剂）和他莫昔芬（TAM;一种ERα/ERβ拮抗剂，也可作为GPR 30激动剂）对海马中乙酰胆碱（ACh）释放的影响，以及用GPR 30拮抗剂G-15阻断17β-雌二醇（E）或TAM作用的能力。请注意，纳入G-1是为了评价选择性激活GPR 30的作用，而纳入TAM是为了区分与GPR 30激活相关的E与ERα或ERβ的作用。本研究旨在测试对钾刺激释放的影响，以及对乙酰胆碱释放刺激喂养。喂养的影响包括，因为我们以前用来证明E对认知性能的有益影响的任务是由食物奖励激发的，我们假设E可能通过增加与奖励相关的ACh释放来提高性能。卵巢切除大鼠治疗1周，并使用在体微透析评估ACh释放。此外，大鼠每天在同一时间喂食数天，并在微透析前禁食过夜。对于每只大鼠，乙酰胆碱释放基础条件下进行了评价，在响应喂养，并在响应钾升高。无论是喂养和高钾增加乙酰胆碱释放海马。在响应喂养，E，G-1，和TAM都显着增加释放的百分比变化。E和TAM的作用被G-15阻断，并且E+TAM组合的作用与E或TAM单独的作用没有显著差异。在响应钾，E，和TAM显着增加ACh释放的百分比变化。G-1的效果稍差。G-15可降低TAM的作用，而E的作用不明显。这些研究结果表明，GPR 30的激活是必要的和足够的帐户与喂养相关的乙酰胆碱释放的E的影响。相反，GPR 30的激活似乎是足够的，但可能不是与钾升高相关的释放增加所必需的。与喂养相关的变化与E，G-1和G-15对先前描述的空间学习任务的获得的影响一致。这些数据证实并扩展了以前的报道，并支持一个假设，即E治疗可以通过激活GPR 30和增强与食物奖励相关的ACh释放来改善特定任务的学习。
We have hypothesized that estradiol enhances basal forebrain cholinergic function and cognitive performance, at least in part, via activation of the novel estrogen receptor GPR30. Here we evaluated the effects of estradiol, G-1 (a selective GPR30 agonist), and tamoxifen (TAM; an ERα/ERβ antagonist that also acts as a GPR30 agonist), on acetylcholine (ACh) release in the hippocampus, as well as the ability to block the effects of 17β-estradiol (E) or TAM with the GPR30 antagonist G-15. Note that G-1 was included to evaluate the effects of selectively activating GPR30, whereas TAM was included to differentiate effects of E associated with activation of GPR30 vs. ERα or ERβ. The study was designed to test effects on potassium-stimulated release, as well as on ACh release stimulated by feeding. Effects of feeding were including because the tasks we used previously to demonstrate beneficial effects of E on cognitive performance were motivated by food reward, and we hypothesized that E may enhance performance by increasing ACh release in association with that reward. Ovariectomized rats were treated for 1 week, and ACh release was evaluated using in vivo microdialysis. In addition, rats were fed at the same time daily for several days and were fasted overnight prior to microdialysis. For each rat, ACh release was evaluated under basal conditions, in response to feeding, and in response to elevated potassium. Both feeding and elevated potassium increased ACh release in the hippocampus. In response to feeding, E, G-1, and TAM all significantly increased the percent change in release. The effects of E and TAM were blocked by G-15, and the effects of combining E+TAM did not differ significantly from the effects of E or TAM alone. In response to elevated potassium, E, and TAM significantly increased the percent change in ACh release. G-1 produced a slightly lesser effect. The effect of TAM was reduced by G-15, but the effect of E was not. These findings suggest that activation of GPR30 is both necessary and sufficient to account for the effects of E on ACh release associated with feeding. In contrast, activation of GPR30 appears to be sufficient, but may not be necessary for increased release associated with elevated potassium. The changes associated with feeding are consistent with the effects of E, G-1 and G-15 on acquisition of a spatial learning task previously described. These data confirm and extend previous reports, and support a hypothesis wherein E treatment can improve learning on specific tasks by activating GPR30 and enhancing ACh release in association with food reward.
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