Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats
Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats
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DOI：
10.1016/j.psyneuen.2006.12.013
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发表时间：
2007-04-01
影响因子：
3.7
通讯作者：
Ramirez, Maria J.
中科院分区：
文献类型：
--
作者：
Aisa, Barbara;Tordera, Rosa;Ramirez, Maria J.
暴露在早期的应激性不良生活事件中可能会增加成人生活中精神病理的易感性。在与压力相关的精神障碍中存在着重要的记忆障碍。因此，人们对了解压力和认知之间相互作用的机制很感兴趣。Mate Wistar大鼠在出生后的前3周(母体分离，MS)经历了每天3小时的分离，成年后在强迫游泳试验中表现出抑郁样行为，下丘脑-垂体-肾上腺(HPA)轴对应激源的反应性增强，下丘脑室旁核(PVN)CRF mRNA表达升高。在MS大鼠海马区，糖皮质激素受体密度较低。MS在Morris水迷宫和新奇物体识别测试(NORT)中都产生了显著的学习障碍。糖皮质激素受体拮抗剂米非司酮和β-肾上腺素能受体拮抗剂心得安。能完全逆转MS大鼠强迫游泳实验中延长的不动时间和NORT中的记忆障碍。我们的数据支持这一假设，即糖皮质激素分泌增加可能与行为有关。以及MS大鼠的认知缺陷。在MS大鼠身上观察到的应激高反应可以至少部分归因于由海马体介导的反馈敏感性受损。糖皮质激素受体。也可以认为去甲肾上腺素系统可能参与了糖皮质激素介导的MS模型的认知损害。(C)2007爱思唯尔有限公司。保留所有权利。
Exposure to early stressful adverse life events may increase vulnerability to psychopathology in adult life. There are important memory disturbances in stress-related psychiatric disorders. Therefore, there is much interest in understanding the mechanisms responsible for interactions between stress and cognition. Mate Wistar rats that experienced 3-h daily separations from the dam during the first 3 weeks of life (maternal separation, MS) showed in adulthood a depressive-like behaviour in the forced swimming test, increased hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and elevated CRF mRNA in the paraventricular nucleus of the hypothalamus (PVN). In the hippocampus of MS rats, there was a lower glucocorticoid receptor density. MS produced significant learning impairments both in the Morris water maze and in the novel object recognition test (NORT). The glucocorticoid receptor antagonist mifepristone and the beta-adrenoceptor antagonist propranolol. were able to completely reverse the increased immobility time in the forced swimming test and the memory deficits in the NORT observed in MS rats. Our data support the hypothesis that elevated secretion of glucocorticoids may be associated to behavioural. and cognitive deficits in MS rats. The stress hyperresponsiveness observed in MS rats could be attributed, at least in part, to an impaired feedback sensitivity mediated by hippocampal. glucocorticoid receptors. It can also be suggested the possible involvement of the noradrenergic system in cognitive impairments mediated by glucocorticoids in the MS model. (c) 2007 Elsevier Ltd. All rights reserved.