PSYCH OpenIR  > 健康与遗传心理学研究室
慢性强迫游泳应激对抑郁行为、B 细胞CLL/淋巴瘤2 关联抗凋亡基因-1 及相关蛋白的影响
Alternative TitleThe effect of chronic forced swim stress on depressive-like behaviors and hippocampal B-cell CLL/lymphoma 2-associated athanogene-1 expression
Thesis Advisor亓晓丽
Degree Grantor中国科学院研究生院
Place of Conferral北京
Degree Discipline心理学
Keyword应激 抑郁 皮质酮 BAG-1 GR ERK1/2 MKP-1
Abstract应激是导致抑郁行为障碍的重要因素,应激导致的下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal, HPA)轴持续亢进和神经可塑性损伤被认为是应激导致抑郁的两大病理机制,但深入的分子机制并不清楚。B 细胞 CLL/淋巴瘤2关联抗凋亡基因1(B-cell CLL/lymphoma 2-associated athanogene-1, BAG-1)作为糖皮质激素受体(glucocorticoid receptor, GR)的共伴侣分子,能够调节决定 HPA轴反应性的GR 受体的功能,也能够调节对神经可塑性起关键作用的细胞外信号蛋白调节激酶(extracellular signal-regulated protein kinase, ERK)信号通路。为此,本研究采用慢性强迫游泳应激抑郁动物模型,初步探讨了应激对抑郁行为及
1 慢性强迫游泳应激导致动物产生抑郁行为,应激动物主要表现探究兴趣降低和快感缺乏。
2 慢性强迫游泳应激显著升高了血浆皮质酮的浓度。
3 慢性强迫游泳应激显著降低了海马细胞核 BAG-1 的表达水平,升高了细胞质BAG-1的表达水平,但对海马 BAG-1的表达水平无显著影响。
4 慢性强迫游泳应激显著降低了海马细胞核GR 的表达水平,但对海马 GR 及细胞质GR 的表达水平无显著影响。  
5 慢性强迫游泳应激显著升高了海马P-ERK1的表达水平,但对P-ERK2、 ERK1/2的表达水平无显著影响。
6 慢性强迫游泳应激显著降低了海马 MKP-1的表达水平。
7 海马细胞核 BAG-1、细胞质 BAG-1、细胞核 GR、MKP-1 的表达水平与抑郁行为多项指标显著相关;海马细胞核BAG-1的表达水平与 MKP-1的表达水平呈显著正相关。
综上所述,应激可能通过降低 BAG-1 的转核活动引起 GR 转核功能障碍和ERK信号通路激活,进而损伤 HPA轴功能和神经可塑性,并最终导致抑郁行为。
Other Abstract   Activation of the hypothalamic-pituitary-adrenal (HPA) axis and alterations of the neuronal plasticity are hypothesized to be the etiology underlying depressive disorders. Stress is the most important factor in the vulnerability to depression, and induces the hyperactivity of the HPA axis and excessive glucocorticoid production, which lead to damages in neuronal plasticities and finally result in depression. B-cell CLL/lymphoma 2-associated athanogene-1(BAG-1), as the co-chaperone molecular of glucocorticoid receptor (GR), can regulate the function of GR, and then affect the HPA axis negative feedback. In addition, BAG-1 can modulate the activity of  the extracellular signal-regulated protein kinase  (ERK) signal pathway, which plays a critical role in the neuronal plasticities. Thus, the aim of the present study was to investigate the possible role of BAG-1 in depressive-like behaviors induced by stress. Chronic forced swim stress was applied to establish animal model of depression. The main results of the study were as follows:
1.  Chronic forced swim stress induced animals to suffer depression which is characterized by decreased exploratory activity and anhedonia.  
2. Chronic forced swim stress significantly increased plasma levels of corticosterone.  
3. Chronic forced swim stress significantly decreased the expression of BAG-1 in the nucleus (NBAG-1)  and increased the expression of BAG-1 in the cytoplasm (CBAG-1) of  hippocampal neurons without  significant  changes of BAG-1 in the whole neurons in hippocampus.
4. Chronic forced swim stress  significantly decreased the expression of GR  in the nucleus of hippocampal neurons (NGR) without  significant changes of GR in the cytoplasm and the whole neurons in hippocampus.
5. Chronic forced swim stress  significantly  increased the levels of P-ERK1 without significant changes of P-ERK2 and ERK1/2 in the hippocampus.
6.  Chronic forced swim stress  significantly decreased the levels of MKP-1  in  the hippocampus.
7. There are significant correlations between the proteins of NBAG-1, CBAG-1, NGR, MKP-1 and some variables of depressive-like behaviors.
In conclusion, chronic forced swim stress decreased the expression  of NBAG-1, decreased GR  tanslocation  in the nucleus  and increased the activity of  P-ERK1 protein in hippocampus. These results suggest that chronic forced stress may destroy the function of the HPA axis and neuronal plasticities and finally induce depression via destroying the tanslocation of GR to nucleus and activating the ERK pathway which resulted from the decreased the transloction of BAG-1 to the nucleus.
Subject Area医学心理学
Document Type学位论文
Recommended Citation
GB/T 7714
秦红宁. 慢性强迫游泳应激对抑郁行为、B 细胞CLL/淋巴瘤2 关联抗凋亡基因-1 及相关蛋白的影响[D]. 北京. 中国科学院研究生院,2014.
Files in This Item:
File Name/Size DocType Version Access License
秦红宁-硕士学位论文.pdf(1995KB)学位论文 限制开放CC BY-NC-SAView Application Full Text
Related Services
Recommend this item
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[秦红宁]'s Articles
Baidu academic
Similar articles in Baidu academic
[秦红宁]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[秦红宁]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 秦红宁-硕士学位论文.pdf
Format: Adobe PDF
All comments (0)
No comment.

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.