GPR30 co-localizes with cholinergic neurons in the basal forebrain and enhances potassium-stimulated acetylcholine release in the hippocampus.
GPR30 co-localizes with cholinergic neurons in the basal forebrain and enhances potassium-stimulated acetylcholine release in the hippocampus.
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DOI：
10.1016/j.psyneuen.2010.07.007
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发表时间：
2011-02
影响因子：
3.7
通讯作者：
Gibbs, R. B.
中科院分区：
文献类型：
--
作者：
Hammond, R.;Nelson, D.;Gibbs, R. B.
GPR30是一种新的膜结合、G蛋白偶联的雌激素受体。我们推测GPR30可能介导了雌二醇对基底前脑胆碱能神经元和认知功能的影响。最近，我们发现G-1，一种选择性的GPR30激动剂，在延迟匹配定位(DMP)T迷宫任务中提高了获得速度。在本研究中，我们研究了GPR30在大鼠前脑中的分布，以及G-1对钾刺激的海马乙酰胆碱释放的影响。在前脑的许多区域，包括海马区、额叶皮质、内侧隔/斜角带、大细胞基底核和纹状体，GPR30免疫反应阳性。GPR30基因在海马区和皮质中的表达水平也高于隔区和纹状体。共定位研究表明，大多数(63%-99%)的前脑胆碱能神经元表达GPR30样免疫反应。低得多的GABA能(含小白蛋白)细胞也含有GPR30(0.4%-35%)。对去卵巢的大鼠持续给予G-1或E2(每天5微克)，与赋形剂处理的对照组相比，钾刺激的海马乙酰胆碱释放增加了近三倍。这些数据表明，GPR30在基底前脑的胆碱能神经元中表达，并提示GPR30的激活增强了海马区的胆碱能功能，类似于E2。这可能解释了此前报道的G-1对DMP收购的影响。
GPR30 is a novel, membrane-bound, G protein-coupled estrogen receptor. We hypothesize that GPR30 may mediate effects of estradiol (E2) on basal forebrain cholinergic neurons and cognitive performance. Recently we showed that G-1, a selective GPR30 agonist, enhances the rate of acquisition on a delayed matching-to-position (DMP) T-maze task. In the present study, we examined the distribution of GPR30 in the rat forebrain, and the effects of G-1 on potassium stimulated acetylcholine release in the hippocampus. GPR30-like immunoreactivity was detected in many regions of the forebrain including the hippocampus, frontal cortex, medial septum/diagonal band of Broca, nucleus basalis magnocellularis, and striatum. GPR30 mRNA also was detected, with higher levels in the hippocampus and cortex than in the septum and striatum. Co-localization studies revealed that the majority (63%–99%) of cholinergic neurons in the forebrain expressed GPR30-like immunoreactivity. A far lower percentage (0.4%–35%) of GABAergic (parvalbumin-containing) cells also contained GPR30. Sustained administration of either G-1 or E2 (5 µg/day) to ovariectomized rats produced a nearly three-fold increase in potassium-stimulated acetylcholine release in the hippocampus relative to vehicle-treated controls. These data demonstrate that GPR30 is expressed by cholinergic neurons in the basal forebrain, and suggest that activation of GPR30 enhances cholinergic function in the hippocampus similar to E2. This may account for the effects of G-1 on DMP acquisition previously reported.
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影响因子：
3.2
作者：
Bohacek, J.;Bearl, A. M.;Daniel, J. M.
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