Qin Yongjun, Karst Henk, Joëls Marian
Section Neurobiology, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands.
J Neurochem. 2004 Apr;89(2):364-74. doi: 10.1111/j.1471-4159.2003.02332.x.
The rat adrenal hormone corticosterone binds to low and high affinity receptors, discretely localized in brain, including the dentate gyrus. Differential activation of the two receptor types under physiological conditions alters gene expression and functional characteristics of hippocampal neurones. In the present study we examined gene expression of electrophysiologically identified dentate granule cells, 1 day after 21 days of unpredictable stress or control treatment, both under basal corticosteroid conditions and after brief in vitro exposure to a high dose of corticosterone. From each cell, RNA was collected, linearly amplified and hybridized with cDNA clones for three calcium channel subunits, four NMDA, two AMPA and 11 GABA receptor subunits. We found that gene expression was not extensively changed after chronic stress when neurones were studied under basal corticosteroid conditions. However, combined with acute exposure to a high corticosterone dose, relative expression of eight transcripts was significantly altered, including a consistent up-regulation of GABAa receptor alpha 1 and down-regulation of calcium channel alpha 1A and alpha 1G subunit expression. If translated to the protein level, this may result in more transient GABAa receptor mediated responses and less transient calcium influx. This could contribute to enhanced excitability and vulnerability of granule cells after chronic stress.
大鼠肾上腺激素皮质酮与低亲和力和高亲和力受体结合，这些受体在大脑中呈离散分布，包括齿状回。在生理条件下，两种受体类型的差异激活会改变海马神经元的基因表达和功能特性。在本研究中，我们检测了经电生理鉴定的齿状颗粒细胞的基因表达情况，这些细胞在经历21天不可预测应激或对照处理1天后，分别处于基础皮质类固醇条件下以及在体外短暂暴露于高剂量皮质酮之后。从每个细胞中收集RNA，进行线性扩增，并与针对三个钙通道亚基、四个N-甲基-D-天冬氨酸（NMDA）、两个α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和11个γ-氨基丁酸（GABA）受体亚基的cDNA克隆进行杂交。我们发现，在基础皮质类固醇条件下研究神经元时，慢性应激后基因表达没有广泛变化。然而，与急性暴露于高剂量皮质酮相结合时，八个转录本的相对表达发生了显著改变，包括GABAa受体α1的持续上调以及钙通道α1A和α1G亚基表达的下调。如果转化为蛋白质水平，这可能导致GABAa受体介导的反应更短暂，钙内流更不短暂。这可能会导致慢性应激后颗粒细胞的兴奋性和易损性增强。
