【摘要】：抑郁癥是一種高發(fā)病率的情感障礙疾病。已有研究發(fā)現(xiàn),抑郁癥的發(fā)生與病人所處的社會(huì)環(huán)境有著極為密切的聯(lián)系。社會(huì)生活中各種各樣的應(yīng)激都可能對(duì)個(gè)體產(chǎn)生心理壓力,心理壓力的長(zhǎng)期累積是導(dǎo)致個(gè)人抑郁的原因之一。研究還表明,抑郁發(fā)生與單胺類(lèi)和谷氨酸系統(tǒng)有著密切的聯(lián)系。谷氨酸作為主要的興奮性神經(jīng)遞質(zhì),在中樞中廣泛分布。很多研究已表明谷氨酸與抑郁癥有著密切的聯(lián)系。關(guān)于谷氨酸與抑郁癥的研究,其中NMDA受體受到了科學(xué)家的高度關(guān)注。有研究顯示谷氨酸NMDA受體的NR2B亞基與多巴胺受體間存在著相互作用,這表明NMDA受體可能對(duì)多巴胺及其受體也有調(diào)節(jié)作用。伏隔核(nucleus accumbens,NAc)是一種與情緒和行為有密切聯(lián)系的核團(tuán),接受多個(gè)腦區(qū)的神經(jīng)元投射,既有谷氨酸能神經(jīng)元,又有多巴胺能神經(jīng)元投射。NAc中的神經(jīng)元主要是GABA能中型多棘神經(jīng)元(MSN)組成,既有谷氨酸受體,也有多巴胺受體的分布。有研究報(bào)道,抗抑郁藥物有增加伏隔核內(nèi)D2受體的作用,而“母愛(ài)剝奪”所建立起的抑郁模型小鼠表明NAc內(nèi)D2受體的nRNA水平的減少。近年來(lái)有較多研究顯示NAc與抑郁的發(fā)生有著密切的聯(lián)系。然而,以往的研究對(duì)NAc中DA給予較多的關(guān)注,而對(duì)谷氨酸及其受體在應(yīng)激性抑郁樣行為發(fā)生中的變化及作用未見(jiàn)報(bào)道。因此,研究應(yīng)激性抑郁樣行為發(fā)生中NMDA受體在NAc中的作用可能有助于我們進(jìn)一步認(rèn)識(shí)抑郁癥的發(fā)生機(jī)制。為了研究應(yīng)激性抑郁樣行為發(fā)生中NAc中谷氨酸及其N(xiāo)MDA受體的變化與作用,本實(shí)驗(yàn)通過(guò)建立慢性不可預(yù)見(jiàn)性溫和應(yīng)激(CUMS)抑郁模型,并采用微量注射的方式向不同組大鼠的NAc區(qū)注射N(xiāo)MDA受體的激動(dòng)劑NMDA及抑制劑MK-801,檢測(cè)各組大鼠間行為差異。使用高效液相色譜(HLPC)、免疫印跡方法(Western blot, WB)分別檢測(cè)大鼠NAc中谷氨酸、NMDA受體NR2B亞基、多巴胺D2受體等分子的在NAc中的變化。實(shí)驗(yàn)結(jié)果如下：1.與正常對(duì)照組相比,CUMS大鼠表現(xiàn)出明顯的快感缺失,探究減少等抑郁樣行為。同時(shí),伴隨NAc中谷氨酸的水平極顯著增加。NR2B亞基的表達(dá)水平未發(fā)生顯著變化。2.與CUMS組大鼠相比較,向正常大鼠NAc區(qū)注射MK-801并不影響動(dòng)物行為。3.NAc微量注射MK-801能改善由CUMS引起的抑郁樣行為,并且會(huì)使NAc中谷氨酸的水平顯著降低,達(dá)到正常組大鼠水平,且NR2B表達(dá)也下降。4. NMDA能夠誘導(dǎo)正常大鼠表現(xiàn)出抑郁樣行為,且NAc中谷氨酸濃度升高。5.在應(yīng)激或注射N(xiāo)MDA、MK-801對(duì)多巴胺D2受體表達(dá)均無(wú)顯著影響。實(shí)驗(yàn)結(jié)果表明,NAc中谷氨酸及其N(xiāo)MDA受體參與了抑郁樣行為的發(fā)生。其機(jī)制主要是應(yīng)激導(dǎo)致的NMDA受體過(guò)度激活。NMDA受體激活對(duì)NAc中的谷氨酸濃度具有正反饋調(diào)節(jié)的作用。正是因?yàn)檫@種相互作用使得NAc中谷氨酸能系統(tǒng)失調(diào),最終導(dǎo)致抑郁樣行為發(fā)生。谷氨酸及其N(xiāo)MDA受體可能并不參與對(duì)多巴胺D2受體表達(dá)的調(diào)節(jié)。
[Abstract]:Depression is a high incidence of affective disorder disease. It has been found that the occurrence of depression is closely related to the social environment of patients. All kinds of stress in social life may produce psychological pressure on individual. The long-term accumulation of psychological stress is one of the causes of individual depression. The study also shows that depression is closely associated with monoamine and glutamate systems. Glutamate, as the main excitatory neurotransmitter, is widely distributed in the central nervous system. Many studies have shown a close link between glutamate and depression. Among the studies on glutamate and depression, NMDA receptors have attracted a great deal of attention from scientists. Some studies have shown the interaction between NR2B subunit of glutamate NMDA receptor and dopamine receptor, which suggests that NMDA receptor may also regulate dopamine and its receptor. The nucleus accumbens nucleus (NAC) is a nucleus closely related to emotion and behavior. It receives neuronal projections from multiple brain regions, including glutaminergic neurons. There are also dopaminergic neurons projecting. NAC neurons are mainly composed of GABA medium polyspinous neurons (MSN), both glutamate receptor and dopamine receptor distribution. It has been reported that antidepressants can increase D2 receptor in nucleus accumbens, and the nRNA level of D2 receptor in NAC is decreased in depressive mice induced by maternal deprivation. In recent years, many studies have shown that NAC is closely related to the occurrence of depression. However, previous studies have paid more attention to DA in NAC, while the changes and roles of glutamate and its receptors in stress-induced depressive behavior have not been reported. Therefore, the study of the role of NMDA receptor in NAC may help us to further understand the mechanism of depression. In order to study the changes and effects of glutamate and its NMDA receptors in NAC during stress-induced depressive behavior, a chronic unpredictable mild stress (CUMS) depression model was established in this study. The NMDA receptor agonist NMDA and its inhibitor MK-801 were injected into the NAC region of different groups by microinjection. The changes of NMDA receptor NR2B subunit and dopamine D2 receptor in NAC were detected by high performance liquid chromatography (HLPC) and Western blotting (WB). The results of the experiment are as follows: 1. Compared with the normal control group, CUMS rats showed obvious loss of pleasure and depressive behavior. At the same time, the level of glutamate in NAC increased significantly. The expression level of NR2B subunit did not change significantly. Compared with CUMS group, injection of MK-801 into NAc region of normal rats had no effect on animal behavior. 3. Microinjection of MK-801 into NAC could improve the depressive behavior induced by CUMS, and decrease the level of glutamate in NAC significantly, reaching the level of normal rats. The expression of NR2B also decreased. NMDA could induce depression-like behavior in normal rats, and the concentration of glutamate in NAC was increased by .5. Neither stress nor injection of NMDA-MK-801 significantly affected the expression of dopamine D 2 receptor. The results showed that glutamate and its NMDA receptor were involved in the development of depressive behavior in NAC. The main mechanism is that stress induced excessive activation of NMDA receptor. NMDA receptor activation has a positive feedback effect on the concentration of glutamate in NAC. It is because of this interaction that the NAC glutaminergic system is dysfunctional, leading to depressive behavior. Glutamate and its NMDA receptors may not be involved in the regulation of dopamine D 2 receptor expression.
【學(xué)位授予單位】：陜西師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R749.4

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相關(guān)期刊論文 前1條

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本文編號(hào)：2122572