Altered protein kinase A in brain of learned helpless rats: Effects of acute and repeated stress
Altered protein kinase A in brain of learned helpless rats: Effects of acute and repeated stress
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DOI：
10.1016/j.biopsych.2004.03.018
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发表时间：
2004-07-01
影响因子：
10.6
通讯作者：
Lyons, J
中科院分区：
文献类型：
--
作者：
Dwivedi, Y;Mondal, AC;Lyons, J
背景：动物中压力诱发的习得性无助 (LH) 是行为抑郁和创伤后应激障碍某些方面的模型。我们检查了 LH 行为是否与蛋白激酶 A (PYA)（一种关键的磷酸化酶）的改变相关，这些改变在不可避免的休克 (IS) 后持续多长时间，以及 IS 的重复是否会延长 LH 行为的磷酸化持续时间和 PYA 的变化。方法：将大鼠在第 1 天或第 1 天暴露于 IS两次，在第1天和第7天。在第1天IS后的第2天和第4天或第1天IS后的第2天、第8天和第14天测试大鼠的逃避潜伏期。测定额叶皮层和海马中的 [H-3]cAMP（环磷酸腺苷）结合、催化活性和 PKA 亚基的表达。结果：在单次 IS 后第 2 天和重复 IS 后第 14 天测试的大鼠中观察到较高的逃避潜伏期。同时，在这些大鼠的大脑中观察到 [H-3]cAMP 结合、PKA 活性以及选择性 PKA RIIbeta 和 Cα 和 Cbeta 亚基的表达降低。结论：重复 IS 延长了 LH 行为的持续时间，并且 LH 行为与 PKA 表观活性和表达的减少有关。 PYA 的减少可能在抑郁症和其他压力相关疾病的病理生理学中至关重要。
Background: Stress-induced learned helplessness (LH) in animals serves as a model of behavioral depression and some aspects of posttraumatic stress disorder, We examined whether LH behavior is associated with alterations in protein kinase A (PYA), a critical phosphorylating enzyme, how long these alterations persist after inescapable shock (IS), and whether repetition of IS prolongs the phosphor duration of LH behavior and changes in PYA.Methods: Rats were exposed to IS eitber on day 1 or twice, on day 1 and day 7. Rats were tested for escape latency on days 2 and 4 after day 1 IS or days 2, 8 and 14 after day 1 and day 7 IS. [H-3]cAMP (cyclic adenosine monophosphate) binding, catalytic activity and expression of PKA subunits were determined in frontal cortex and hippocampus.Results: Higher escape latencies were observed in rats tested on day 2 after single IS and on day 14 after repeated IS. Concurrently, reduced [H-3]cAMP binding, PKA activity, and expression of selective PKA RIIbeta and Calpha and Cbeta subunits were observed in the brains of these rats.Conclusions: Repeated IS prolongs the duration of LH behavior, and LH behavior is associated with reductions in apparent activity and expression of PKA. These reductions in PYA may be critical in the pathophysiology of depression and other stress-related disorders.