Effects of chronic social defeat stress on MAP kinase cascade
Effects of chronic social defeat stress on MAP kinase cascade
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DOI：
10.1016/j.neulet.2011.09.047
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发表时间：
2011-10-31
影响因子：
2.5
通讯作者：
Toyoda, Atsushi
中科院分区：
文献类型：
--
作者：
Iio, Wataru;Matsukawa, Noriko;Toyoda, Atsushi
慢性心理和社会压力会导致人类精神疾病。在这项研究中，我们分析了长期社交失败大鼠海马体中丝裂原激活蛋白激酶（MAPK）级联反应。连续 5 周每天遭受社交失败的大鼠表现出生理和行为变化，包括体重增加率降低、肾上腺增大以及强迫游泳测试中的不动性增加，但在旷场测试中运动活动没有随之变化。体重改变和肾上腺增大是人类抑郁症的典型症状。在强迫游泳测试中长时间不动表明行为绝望，这是一种公认的抑郁指数。由于 MAPK 级联在抑郁症中发挥着关键作用，因此我们使用蛋白质印迹分析定量了这些分子在长期失败大鼠海马中的表达。我们发现，与对照组相比，慢性失败大鼠海马区的磷酸化 MAPK 激酶 1/2 (MEK1/2) 和磷酸化细胞外信号调节激酶 1/2 (ERK1/2) 减少，而 MAPK 磷酸酶-1 (MKP-1) 增加。这些结果与抑郁症患者和其他抑郁症动物模型的研究结果一致。总之，我们的研究结果表明，Wistar 大鼠的慢性心理社会压力会诱发抑郁样行为，并下调海马中的 MAPK 级联反应。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Chronic psychological and social stress can cause psychiatric disorders in humans. In this study, we analyzed the mitogen-activated protein kinase (MAPK) cascade in the hippocampus of chronically socially defeated rats. The rats that were subjected to social defeat every day for 5 weeks showed physiological and behavioral changes, including a reduced rate of weight gain, enlarged adrenal glands, and increased immobility in the forced swim test without concomitant changes in locomotor activity in the open field test. Altered body weight and enlarged adrenal glands are typical symptoms of human depression. Prolonged immobility in the forced swim test indicates behavioral despair, a well-established index of depression. Because the MAPK cascade plays a pivotal role in depression, we quantified the expression of these molecules in the hippocampus of chronically defeated rats using western blot analysis. We found that phospho-MAPK kinases 1/2 (MEK1/2) and phospho-extracellular signal-regulated kinases 1/2 (ERK1/2) were decreased, whereas MAPK phosphatase-1 (MKP-1) was increased in the hippocampus of chronically defeated rats compared to the control group. These results were consistent with findings in depressed patients and other animal models of depression. In conclusion, our findings suggest that chronic psychosocial stress in Wistar rats induced depression-like behavior and downregulated the MAPK cascade in the hippocampus. (C) 2011 Elsevier Ireland Ltd. All rights reserved.