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糖皮质激素受体及其分子伴侣热休克蛋白90在应激所致抑郁行为中作用的探讨
Alternative TitleThe association of glucocorticoid receptor with heat-shock protein(HSP) 90 in rat hippocampus is correlated with the depressive behaviors following chronic forced swim stress
孙萌
2008-09
Publication Place北京
Contribution Rank1
Abstract

抑郁症是一种以情绪低落、思维迟钝、行为迟缓为主要症状的精神疾病。众多的研究表明慢性不可控制的应激是其产生的重要原因。机体慢性应激反应将会导致血浆糖皮质激素(glucocorticoid, GC)水平增高以及HPA轴对其反馈调节能力的减弱。糖皮质激素受体(glucocorticoid receptor, CR)分布于多种淋巴组织及脑的各处,海马神经元的CSR受体是应激激素作用的主要靶点,是糖皮质激素反馈形成的基础,可以调整HPA轴的活动。为此本实验应用慢性强迫游泳应激建立动物抑郁模型,来探讨慢性应激所致抑郁行为与海马神经元细胞中GR核转移效率及其分子伴侣HSP90的表达分布的关系;阐明在应激所致抑郁行为中,海马神经元中GR功能与分子伴侣HSP90以及细胞能量代谢的因果关系。

结果显示慢性强迫游泳应激导致动物产生明显的抑郁样行为反应。应激动物海马神经元中,GR细胞质和细胞核中分布异常,在细胞核中含量相比对照组增高,并且在整个细胞中HSP90与GR的结合量降低。这与检测到的应激组动物海马神经元中GR核转率异常关系密切。本实验中应激组实验动物海马神经元中ATP/ADP的比率相比对照组动物明显降低,而HSP90作为衡量细胞能量水平的分子传感器,对细胞中ATP/ADP的比率非常敏感,ATP/ADP的比率的下降会成倍影响HSP90的生物活性。

从本实验研究中,可以推论慢性应激诱导的糖皮质激素皮质酮(corticosterone, CORT)升高,可以导致海马神经细胞能量代谢衰减和细胞内能量状态低下,影响GR分子伴侣HSP90的生物活性,降低HSP90和GR的结合率,进而影响GR核穿梭效率和功能,导致GC反馈调节抑制异常。

Other Abstract

In the cast of major depression, a clinical disorder is characterized by significant alterations in mood neurovegetative function and cognition. There is growing evidence that chronic stress is one of the most important factors in the vulnerability to depression. One of the most reliably reported neurobiological alterations in major depression is both high level of glucocorticoid (GC) and impaired HPA axis glucocorticoid feedback sensitivity. The glucocorticoid receptor (GR) is widely distributed in hypothalamus and hippocampus, with responsibility to the HPA axis glucocorticoid feedback sensitivity. In this study, the GR translocation and the distribution in cytoplasm and nucleus were examined, in order to illustrate the relationship between the GR, HSP90 and the cellular energy metabolism in depressive-like behaviors induced by stress. The results showed that chronic forced swim stress induced animals to suffer depression and in the hippocampal neurons of stressed animals, the concentration of GR in nucleus was higher than the control. Moreover, the content of HSP90 combined with GR in hippocampal neurons of stressed animals decreased compared with the control, which was correlated with the abnormal translocation of CR from the cytoplasm to the nuclease.

In this studythe ratio of ATP/ADP in hippocampal neurons of stressed animals also decreased compared with the controls, which lead to the reduction of the function of HSP90. From the results, it can be speculated that chronic stress induced the increased concentrations of GC, leading to the reduced energy levels and energy deregulation in hippocampal neurons. Lowering ATP level in hippocampus can trigger dissociation of Hsp90 from GR and degradation of GR function which may contribute to the HPA axis glucocorticoid feedback insensitivity.

Keyword应激 抑郁症 海马 糖皮质激素受体 热休克蛋自90
Pages52
Language中文
Document Type科技报告
Identifierhttp://ir.psych.ac.cn/handle/311026/29207
Collection健康与遗传心理学研究室
Affiliation中国科学院心理研究所
Recommended Citation
GB/T 7714
孙萌. 糖皮质激素受体及其分子伴侣热休克蛋白90在应激所致抑郁行为中作用的探讨[R]. 北京,2008.
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