van Gemert N G, Joëls M
Swammerdam Institute for Life Sciences, Center for NeuroScience, University of Amsterdam, Kruislaan, Amsterdam, The Netherlands.
J Neuroendocrinol. 2006 Oct;18(10):732-41. doi: 10.1111/j.1365-2826.2006.01472.x.
Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the present study, we examined: (i) whether these changes in expression are accompanied by altered Ca2+ currents in rat dentate granule cells recorded on day 22 and (ii) whether treatment with the glucocorticoid receptor antagonist mifepristone during the last 4 days of the stress protocol normalises the putative stress-induced effects. Three weeks of unpredictable stress did not affect Ca2+ current amplitude in dentate granule cells under basal conditions (i.e. after incubation with vehicle solution). However, the sustained Ca2+ current component (which largely depends on the alpha1C subunit) was significantly increased in amplitude after chronic stress when slices had been treated with corticosterone 1-4 h before recording. These findings suggest that dentate granule cells are exposed to an increased calcium load after exposure to an acute stressor when they have a history of chronic stress, potentially leading to increased vulnerability of the cells. The present results are in line with the molecular data on Ca2+ channel alpha1C subunit expression. A significant three-way interaction between chronic stress, corticosterone application and mifepristone treatment was found, indicating that the combined effect of stress and corticosterone depends on mifepristone cotreatment. Interestingly, current density (defined as total current divided by capacitance) did not differ between the groups. This indicates that the observed changes in Ca2+ current amplitude could be attributable to changes in cell size.
慢性不可预测应激会影响大鼠大脑的多种特性。在齿状回中，除其他因素外，在经历21天不可预测应激并同时急性应用皮质酮（100 nM）后，已发现Ca2+通道α1C亚基的mRNA表达增加。在本研究中，我们检测了：（i）这些表达变化是否伴随着在第22天记录的大鼠齿状颗粒细胞中Ca2+电流的改变，以及（ii）在应激方案的最后4天用糖皮质激素受体拮抗剂米非司酮治疗是否能使假定的应激诱导效应恢复正常。三周的不可预测应激在基础条件下（即与溶媒溶液孵育后）并未影响齿状颗粒细胞中的Ca2+电流幅度。然而，当切片在记录前1 - 4小时用皮质酮处理时，慢性应激后持续的Ca2+电流成分（其很大程度上依赖于α1C亚基）的幅度显著增加。这些发现表明，当齿状颗粒细胞有慢性应激史时，在暴露于急性应激源后会面临增加的钙负荷，这可能导致细胞的易损性增加。目前的结果与关于Ca2+通道α1C亚基表达的分子数据一致。发现慢性应激、皮质酮应用和米非司酮治疗之间存在显著的三因素交互作用，表明应激和皮质酮的联合效应取决于米非司酮的共同处理。有趣的是，各组之间的电流密度（定义为总电流除以电容）没有差异。这表明观察到的Ca2+电流幅度变化可能归因于细胞大小的变化。
