Analysis of the stress response in rats trained in the water-maze:: Differential expression of corticotropin-releasing hormone, CRH-R1, glucocorticoid receptors and brain-derived neurotrophic factor in limbic regions
Analysis of the stress response in rats trained in the water-maze:: Differential expression of corticotropin-releasing hormone, CRH-R1, glucocorticoid receptors and brain-derived neurotrophic factor in limbic regions
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DOI：
10.1159/000093129
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发表时间：
2005-01-01
影响因子：
4.1
通讯作者：
Joseph-Bravo, Patricia
中科院分区：
文献类型：
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作者：
Aguilar-Valles, Argel;Sanchez, Edith;Joseph-Bravo, Patricia
Glucocorticoids and corticotropin-releasing hormone (CRH) are key regulators of stress responses.不同类型的压力会激活CRH系统；在下丘脑中，CRH 表达和释放会因身体或心理压力而增加，而在杏仁核中，CRH 表达和释放会优先因心理压力而增加。学习和记忆过程受到不同水平的糖皮质激素和压力的调节。为了表征空间学习等海马依赖性任务引起的压力类型，我们比较了杏仁核、海马和下丘脑中糖皮质激素受体 (GR)、pro-CRH 和 CRH-R1 mRNA 的表达谱（通过 RT-PCR 分析），并通过放射免疫测定在不同训练阶段量化了血清皮质酮水平。由于脑源性神经营养因子（BDNF）在学习和记忆过程中的突出作用，其 mRNA 水平也被量化。在 Morris 水迷宫（每天 10 次试验）中训练 1、3 或 5 天的雄性 Wistar 大鼠在最后一次试验后 5-60 分钟处死。第一天，带轭动物和受过训练的动物均出现强烈的应激反应（皮质酮和下丘脑 pro-CRH 和 CRH-R1 mRNA 水平增加）；随着测试的进行，变化逐渐减弱。在带轭和受过训练的动物中，当压力最高时，杏仁核中 CRH 前体 mRNA 水平下降，而 BDNF mRNA 水平增加。无论是带轭组还是训练组，海马的 GR mRNA 水平在第 1 天和第 3 天下降，到第 5 天恢复正常，而 pro-CRH 和 CRH-R1 水平在第 3 天后增加。自第 3 天起，仅海马 BDNF 基因表达增加，特别是由于空间学习所致。这些结果表明，Morris 水迷宫范式诱导了强烈的应激反应，该反应逐渐减弱。杏仁核中 CRH 表达的抑制表明所造成的压力是身体性的，而不是心理性的，并且可能会减少恐惧或焦虑。版权所有 (c) 2005 S. Karger AG，巴塞尔。
Glucocorticoids and corticotropin-releasing hormone (CRH) are key regulators of stress responses. Different types of stress activate the CRH system; in hypothalamus, CRH expression and release are increased by physical or psychological stressors while in amygdala, preferentially by psychological stress. Learning and memory processes are modulated by glucocorticoids and stress at different levels. To characterize the kind of stress provoked by a hippocampal-dependent task such as spatial learning, we compared the expression profile of glucocorticoid receptor (GR), pro-CRH and CRH-R1 mRNAs (analyzed by RT-PCR), in amygdala, hippocampus and hypothalamus and quantified serum corticosterone levels by radioimmunoassay at different stages of training. mRNA levels of brain-derived neurotrophic factor (BDNF) were also quantified due to its prominent role in learning and memory processes. Male Wistar rats trained for 1, 3 or 5 days in the Morris water-maze (10 trials/day) were sacrificed 5-60 min the after last trial. A strong stress response occurred at day one in both yoked and trained animals (increased corticosterone and hypothalamic pro-CRH and CRH-R1 mRNA levels); changes gradually diminished as the test progressed. In amygdala, pro-CRH mRNA levels decreased while those of BDNF augmented when stress was highest, in yoked and trained animals. Hippocampi, of both yoked and trained groups, had decreased levels of GR mRNA on days 1 and 3, normalizing by day 5, while those of pro-CRH and CRH-R1 increased after the 3rd day. Increased gene expression, specifically due to spatial learning, occurred only for hippocampal BDNF since day 3. These results show that the Morris water-maze paradigm induces a strong stress responsethat is gradually attenuated. Inhibition of CRH expression in amygdala suggests that the stress inflicted is of physical but not of psychological nature and could lead to reduced fear or anxiety. Copyright (c) 2005 S. Karger AG, Basel.