本文選題：抑郁 + 慢性應激抵抗力��； 參考：《青島大學》2017年碩士論文

【摘要】：目的 重度抑郁癥是一種常見的情緒障礙性疾病,其主要特征是長期情緒低落,興趣和快感缺失,自我評估低下。抑郁癥的發(fā)病機制復雜,但是慢性應激被認為是導致抑郁癥發(fā)生的主要致病因素,能夠導致多巴胺系統(tǒng)功能異常、腦源性神經(jīng)營養(yǎng)因子(BDNF)減少、垂體-下丘腦-腎上腺軸(HPA軸)損傷,最終引起獎賞系統(tǒng)GABA能神經(jīng)元受損。然而大多數(shù)個體經(jīng)歷慢性應激后并沒有遭受重度抑郁癥的困擾,即表現(xiàn)出對慢性應激的抵抗。邊緣系統(tǒng)GABA能神經(jīng)元對于慢性應激為易感個體而且其損傷與重度抑郁癥有關,然而這些神經(jīng)元在受慢性應激損傷的同時是否也涉及抗慢性應激誘導抑郁癥的內(nèi)在機制還尚不清楚。伏隔核作為邊緣系統(tǒng)的一部分,其內(nèi)的神經(jīng)元主要是GABA能神經(jīng)元,同時它還參與獎賞環(huán)路的組成,其損傷也與快感缺失行為的發(fā)生和發(fā)展有關。因此我們提出研究伏隔核GABA能神經(jīng)元是否涉及抗慢性應激誘導抑郁癥的內(nèi)源性抗抑郁機制。方法 首先給予實驗組小鼠為期3周的慢性不可預測的溫和應激(CUMS)處理,根據(jù)它們在糖水偏嗜度實驗、Y迷宮實驗以及強迫游泳實驗中是否有顯著的行為改變來確定抑郁樣行為和慢性應激抵抗行為,在這三個實驗中均表現(xiàn)出顯著的行為改變的小鼠被定義為CUMS誘導的抑郁樣小鼠,而均無顯著的行為改變的則被定義為慢性應激抵抗小鼠。其次運用全細胞膜片鉗電生理技術記錄并研究CUMS誘導的抑郁樣小鼠、慢性應激抵抗組小鼠和對照組小鼠伏隔核GABA能神經(jīng)元功能的變化。結果 我們得到的實驗結果如下:1 慢性不可預測的溫和刺激(CUMS)能誘導產(chǎn)生抑郁樣行為小鼠或慢性應激抵抗小鼠;2 CUMS誘導的抑郁樣小鼠伏隔核GABA能神經(jīng)元對抑制性神經(jīng)遞質GABA的釋放減少,即信息輸出能力降低,而慢性應激抵抗組小鼠伏隔核GABA能神經(jīng)元信息輸出能力沒有變化;3 CUMS誘導的抑郁樣小鼠伏隔核GABA能神經(jīng)元發(fā)放連續(xù)動作電位的能力降低,即興奮性降低,而慢性應激抵抗組小鼠伏隔核GABA能神經(jīng)元興奮性無變化;4 CUMS誘導的抑郁樣小鼠伏隔核GABA能神經(jīng)元對興奮性神經(jīng)遞質的接收減少,即興奮性輸入能力降低,而慢性應激抵抗組小鼠伏隔核GABA能神經(jīng)元興奮性輸入能力增加。即抑郁樣小鼠伏隔核GABA能神經(jīng)元的功能整體表現(xiàn)出下調的狀態(tài),而慢性應激抵抗小鼠GABA能神經(jīng)元的功能正常甚至上調。因而,伏隔核GABA能神經(jīng)元的功能狀態(tài)與個體對慢性應激的敏感性和抵抗性有關。結論 伏隔核GABA能神經(jīng)元的損傷與重度抑郁癥有關,伏隔核GABA能神經(jīng)元涉及抗慢性應激誘導抑郁癥的內(nèi)源性抗抑郁機制。
[Abstract]:Objective severe depression is a common disorder, which is characterized by chronic depression, lack of interest and pleasure, and low self-assessment. The pathogenesis of depression is complex, but chronic stress is thought to be the main cause of depression, which can lead to abnormal dopamine system function and decrease of brain-derived neurotrophic factor (BDNF). The damage of pituitary-hypothalamic-adrenal axis leads to the damage of GABA neurons in the reward system. However, most individuals did not suffer from severe depression after chronic stress, that is, they showed resistance to chronic stress. GABA neurons in the limbic system are susceptible to chronic stress and their damage is associated with severe depression. However, it is not clear whether these neurons are involved in the underlying mechanism of chronic stress-induced depression as well as chronic stress damage. As a part of the marginal system, nucleus accumbens is mainly composed of GABA neurons, and it is also involved in the composition of reward loop, and its damage is related to the occurrence and development of pleasure loss behavior. Therefore, we propose to investigate whether GABA neurons in nucleus accumbens are involved in the endogenous antidepressant mechanism of chronic stress-induced depression. Methods the mice in the experimental group were treated with chronic unpredictable mild stress (CUMS) for 3 weeks. Based on whether they had significant behavioral changes in the sugar water bias test, the Y-maze test and the forced swimming test, they were used to determine depressive behavior and chronic stress resistance. In these three experiments, the mice with significant behavioral changes were defined as CUMS induced depressive mice, while those without significant behavioral changes were defined as chronic stress resistant mice. Secondly, whole-cell patch clamp electrophysiological technique was used to record and study the changes of GABA neurons in the nucleus accumbens of depressive mice induced by CUMS, chronic stress resistance group and control group. Results the experimental results were as follows: 1. Chronic unpredictable mild stimulation (CUMS) could induce depression like behavior in mice or depressive septal nucleus GABA neurons induced by 2 CUMS in chronic stress resistant mice. The release of neurotransmitter GABA was decreased. That is, the ability of information output decreased, but the ability of information output of GABA neurons in nucleus accumbens of chronic stress resistance group did not change. The ability of releasing continuous action potential of GABA neurons in nucleus accumbens of depressive mice induced by 3 CUMS was decreased, that is, the excitability was decreased. In chronic stress resistance group, the excitability of GABA neurons in nucleus accumbens was not changed. The GABA neurons in the nucleus accumbens induced by 4 CUMS decreased the reception of excitatory neurotransmitters, that is, the ability of excitatory input decreased. In chronic stress resistance group, the excitatory input ability of GABA neurons in nucleus accumbens was increased. That is, the function of GABA neurons in the nucleus accumbens of depressive mice was down-regulated as a whole, while the function of GABA neurons in chronic stress resistant mice was normal or upregulated. Therefore, the functional state of GABA neurons in nucleus accumbens is related to the sensitivity and resistance of individuals to chronic stress. Conclusion the damage of GABA neurons in nucleus accumbens is related to severe depression. GABA neurons in nucleus accumbens are involved in the endogenous antidepressant mechanism of chronic stress-induced depression.
【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.4

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本文編號：1986112