Dehydroepiandrosterone sulfate and estrone sulfate reduce GABA-recurrent inhibition in the hippocampus via muscarinic acetylcholine receptors.
Dehydroepiandrosterone sulfate and estrone sulfate reduce GABA-recurrent inhibition in the hippocampus via muscarinic acetylcholine receptors.
复制标题
硫酸脱氢表雄酮和硫酸雌酮通过毒蕈碱乙酰胆碱受体减少海马中 GABA 的反复抑制。
DOI：
10.1002/hipo.20232
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发表时间：
2006
期刊：
影响因子：
3.5
通讯作者：
Allison,DavidW
中科院分区：
文献类型：
--
作者：
Steffensen,ScottC;Jones,MarcD;Hales,Kimberly;Allison,DavidW
最近的几项研究已经确定雌激素在改善特定的神经退行性疾病中的作用，主要是那些与基底前脑的胆碱能神经元及其在皮质和海马区的靶点有关的退行性疾病。我们先前已经证明，内源性和外源性应用神经类固醇脱氢表雄酮硫酸盐(DHEAS)显著减少GABA介导的反复抑制，并使海马区单位活动与theta节律同步(Steffensen(1995)海马区5：320-328)。在这项研究中，我们评估了毒碱受体在介导DHEAS和人类主要循环雌激素硫酸雌酮(ES)对大鼠海马齿状回和CA1亚区短潜伏期诱发电位反应、双脉冲抑制(PPI)、双脉冲促进和GABA中间神经元活动的影响中的作用。M2型胆碱能受体激动剂顺式二氧戊烷、DHEAS和ES的原位微电泳法显著降低了齿状回和CA1区的PPI，该作用可被M2受体拮抗剂加拉明所阻断。与DHEAS相似，微电泳法注射ES可增加群体峰电位幅度，但不增加兴奋性传递，但这种作用不能被加拉胺阻断。微电泳法应用顺式二氧戊烷和ES可明显增加齿状回门区和CA1区神经元的放电频率，并增强它们与海马theta节律的同步性。这些结果表明，选择性的GABA调节神经类固醇和神经活性雌激素硫酸盐改变了隔-海马GABA能中间神经元的胆碱能调节，介导了对海马主细胞活动的反复抑制，而不是前馈抑制。©2006 Wiley-Liss，Inc.
Several recent studies have established a role for estrogens in ameliorating specific neurodegenerative disorders, mainly those associated with the cholinergic neurons of the basal forebrain and their targets in the cortex and hippocampus. We have previously demonstrated that endogenous and exogenous application of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) markedly reduces GABA‐mediated recurrent inhibition and synchronizes hippocampal unit activity to theta rhythm (Steffensen (1995) Hippocampus 5:320–328). In this study, we evaluated the role of muscarinic receptors in mediating the effects of DHEAS and estrone sulfate (ES), the principal circulating estrogen in humans, on short‐latency‐evoked potential responses, paired‐pulse inhibition (PPI), paired‐pulse facilitation, and GABA interneuron activity in the dentate gyrus and CA1 subfields of the rat hippocampus. In situ microelectrophoretic application of the muscarinic M2 subtype cholinergic receptor agonist cis‐dioxolane, DHEAS, and ES markedly reduced PPI in the dentate and CA1 that was blocked by the M2 receptor antagonist gallamine. Similar to DHEAS, microelectrophoretic administration of ES increased population spike amplitudes, without increasing excitatory transmission, but this effect was not blocked by gallamine. Microelectrophoretic application of cis‐dioxolane and ES markedly increased the firing rate of dentate hilar interneurons and CA1 oriens/alveus interneurons and enhanced their synchrony to hippocampal theta rhythm. These findings suggest that select GABA‐modulating neurosteroids and neuroactive estrogen sulfates alter septohippocampal cholinergic modulation of hippocampal GABAergic interneurons mediating recurrent, but not feedforward, inhibition of hippocampal principal cell activity. © 2006 Wiley‐Liss, Inc.