Karst Henk, Joëls Marian
SILS-CNS, University of Amsterdam, Amsterdam, The Netherlands.
Neuropsychopharmacology. 2007 Aug;32(8):1830-9. doi: 10.1038/sj.npp.1301296. Epub 2007 Jan 17.
Chronic stress alters many properties in rat brain, like serotonin responsiveness and dendritic morphology. In the present study, we examined (i) whether unpredictable stress during 21 days affects calcium (Ca) currents of CA1 pyramidal neurons recorded on day 22; and (ii) if so, whether this change is normalized by treatment with the glucocorticoid receptor-antagonist RU 38486 during days 18-21. At 3 weeks of unpredictable stress increased the amplitude of the peak and sustained calcium current components, determined in hippocampal slices prepared from animals under rest (ie, with low corticosterone levels). The increased Ca-current amplitude was associated with an enhanced cell capacitance; current density was not significantly affected by chronic stress. In slices from stressed rats that received RU 38486, no stress-induced enhancement of calcium current amplitude was seen, while RU 38486 by itself did not alter calcium currents in handled controls. We confirmed earlier observations that brief in vitro treatment with 100 nM corticosterone, thus substantially activating the low-affinity glucocorticoid receptors, increases Ca-current amplitude recorded 1-4 h later in slices from naïve rats. However, Ca-current amplitude was not affected by corticosterone applied to slices from handled controls and currents were even decreased by corticosterone given to slices from chronically stressed rats, suggesting that corticosterone effects depend on the history of the animal. In conclusion, the data indicate that chronic stress, RU 38486 treatment as well as acute rises in corticosterone level strongly modulate calcium influx into CA1 neurons. This could have consequences for the viability of these neurons.
慢性应激会改变大鼠大脑中的许多特性，如血清素反应性和树突形态。在本研究中，我们检测了：（i）21天的不可预测应激是否会影响在第22天记录的CA1锥体神经元的钙（Ca）电流；以及（ii）如果是这样，在第18 - 21天用糖皮质激素受体拮抗剂RU 38486治疗是否能使这种变化恢复正常。在3周的不可预测应激下，静息状态（即皮质酮水平较低）动物制备的海马切片中，峰值和持续钙电流成分的幅度增加。钙电流幅度增加与细胞电容增强有关；慢性应激对电流密度没有显著影响。在接受RU 38486的应激大鼠切片中，未观察到应激诱导的钙电流幅度增强，而RU 38486本身并未改变处理过的对照大鼠的钙电流。我们证实了早期的观察结果，即100 nM皮质酮的短暂体外处理，从而充分激活低亲和力糖皮质激素受体，会增加在未处理大鼠切片中1 - 4小时后记录的钙电流幅度。然而，皮质酮应用于处理过的对照大鼠的切片时，钙电流幅度不受影响，而应用于慢性应激大鼠的切片时，电流甚至会降低，这表明皮质酮的作用取决于动物的经历。总之，数据表明慢性应激、RU 38486治疗以及皮质酮水平的急性升高强烈调节钙流入CA1神经元。这可能会对这些神经元的存活产生影响。
