Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity
Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity
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DOI：
10.1073/pnas.0503878102
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发表时间：
2006-01-03
影响因子：
11.1
通讯作者：
Schütz, G
中科院分区：
文献类型：
--
作者：
Berger, S;Wolfer, DP;Schütz, G
皮质类固醇在大脑中的作用是由盐皮质激素(MR)和糖皮质激素(GR)受体介导的。MR和GR中介效应中的干扰被认为损害认知、行为和内分泌控制。为了评估边缘MR在这些过程中的功能，我们使用Cre/loxP重组系统使小鼠前脑中的MR基因失活。我们在各种学习和探索测试中筛选出边缘MR缺陷的小鼠。突变小鼠表现出对水迷宫任务的学习障碍，以及由于行为毅力和刻板印象而在放射状迷宫上的工作记忆测量方面的缺陷。他们对一个新奇的物体表现出一种高反应性，但表现出正常的焦虑样行为。这些行为改变与苔藓纤维投射异常和海马区GR表达上调有关。成年突变小鼠在昼夜节律低谷和高峰期皮质酮水平正常。这一遗传模型提供了关于边缘MR和GR之间永久平衡改变的后果的重要信息，并暗示了与应激相关的神经内分泌和神经精神疾病。
Corticosteroid action in the brain is mediated by the mineralocorticoid (MR) and the glucocorticoid (GR) receptor. Disturbances in MR- and GR-mediated effects are thought to impair cognition, behavior, and endocrine control. To assess the function of the limbic MR in these processes, we inactivated the MR gene in the forebrain of the mouse using the Cre/loxP-recombination system. We screened the mice with a limbic MR deficiency in various learning and exploration tests. The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy. They exhibit a hyperreactivity toward a novel object but normal anxiety-like behavior. The behavioral changes are associated with abnormalities of the mossy fiber projection and an up-regulation of GR expression in the hippocampus. Adult mutant mice show normal corticosterone levels at circadian trough and peak. This genetic model provides important information about the consequences of a permanently altered balance between limbic MR and GR, with implications for stress-related neuroendocrine and neuropsychiatric diseases.