Meyer J H, Lee S, Wittenberg G F, Randall R D, Gruol D L
Department of Neuropharmacology and Alcohol Research Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Neuroscience. 1999;90(4):1177-83. doi: 10.1016/s0306-4522(98)00543-0.
The effect of the neurosteroid dehydroepiandrosterone sulfate on inhibitory synaptic transmission was studied in area CA1 of the rat hippocampus using an in vitro hippocampal slice preparation. Synaptic responses elicited by stimulation of Schaffer collateral fibers were recorded extracellularly as population spikes in the somatic region and as synaptic field potentials in the dendritic region. Bath application of dehydroepiandrosterone sulfate (10 microM) enhanced the synaptically evoked somatic population spike with no effect on the dendritic synaptic potential. Isolation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor-mediated component of the synaptic response by addition of antagonists of N-methyl-D-aspartate and GABA receptors to the perfusion saline demonstrated that dehydroepiandrosterone sulfate had no effect on this component of the dendritic synaptic potential. In contrast, dehydroepiandrosterone sulfate antagonized GABA receptor-mediated inhibitory effects in the somatic region, resulting in an augmentation of the somatic population spike amplitude. Paired-pulse facilitation was unaltered by dehydroepiandrosterone sulfate, thus arguing against possible presynaptic sites of dehydroepiandrosterone sulfate's actions. These results indicate that dehydroepiandrosterone sulfate can alter synaptic transmission in the hippocampus through selective postsynaptic actions on inhibitory synaptic transmission. A synaptic effect of dehydroepiandrosterone sulfate is consistent with a neuromodulatory role for this neurosteroid in the central nervous system, and may contribute to the reported effects of dehydroepiandrosterone sulfate on cognitive processes such as learning and memory.
使用体外海马脑片制备技术，研究了神经甾体硫酸脱氢表雄酮对大鼠海马CA1区抑制性突触传递的影响。刺激海马Schaffer侧支纤维引发的突触反应，在体细胞区域以群体峰电位形式、在树突区域以突触场电位形式进行细胞外记录。浴槽应用硫酸脱氢表雄酮（10微摩尔）增强了突触诱发的体细胞群体峰电位，而对树突突触电位无影响。通过向灌注盐水中添加N-甲基-D-天冬氨酸和GABA受体拮抗剂，分离出突触反应中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体介导的成分，结果表明硫酸脱氢表雄酮对树突突触电位的这一成分无影响。相反，硫酸脱氢表雄酮拮抗了体细胞区域GABA受体介导的抑制作用，导致体细胞群体峰电位幅度增大。硫酸脱氢表雄酮对配对脉冲易化无影响，因此排除了硫酸脱氢表雄酮作用于突触前位点的可能性。这些结果表明，硫酸脱氢表雄酮可通过对抑制性突触传递的选择性突触后作用来改变海马中的突触传递。硫酸脱氢表雄酮的突触效应与其在中枢神经系统中的神经调节作用一致，可能有助于解释硫酸脱氢表雄酮对学习和记忆等认知过程的影响。
