抑郁条件下伏隔核中谷氨酸及其NMDA受体对情绪和行为的调节
发布时间：2018-07-14 18:25
【摘要】：抑郁症是一种高发病率的情感障碍疾病。已有研究发现,抑郁症的发生与病人所处的社会环境有着极为密切的联系。社会生活中各种各样的应激都可能对个体产生心理压力,心理压力的长期累积是导致个人抑郁的原因之一。研究还表明,抑郁发生与单胺类和谷氨酸系统有着密切的联系。谷氨酸作为主要的兴奋性神经递质,在中枢中广泛分布。很多研究已表明谷氨酸与抑郁症有着密切的联系。关于谷氨酸与抑郁症的研究,其中NMDA受体受到了科学家的高度关注。有研究显示谷氨酸NMDA受体的NR2B亚基与多巴胺受体间存在着相互作用,这表明NMDA受体可能对多巴胺及其受体也有调节作用。伏隔核(nucleus accumbens,NAc)是一种与情绪和行为有密切联系的核团,接受多个脑区的神经元投射,既有谷氨酸能神经元,又有多巴胺能神经元投射。NAc中的神经元主要是GABA能中型多棘神经元(MSN)组成,既有谷氨酸受体,也有多巴胺受体的分布。有研究报道,抗抑郁药物有增加伏隔核内D2受体的作用,而“母爱剥夺”所建立起的抑郁模型小鼠表明NAc内D2受体的nRNA水平的减少。近年来有较多研究显示NAc与抑郁的发生有着密切的联系。然而,以往的研究对NAc中DA给予较多的关注,而对谷氨酸及其受体在应激性抑郁样行为发生中的变化及作用未见报道。因此,研究应激性抑郁样行为发生中NMDA受体在NAc中的作用可能有助于我们进一步认识抑郁症的发生机制。为了研究应激性抑郁样行为发生中NAc中谷氨酸及其NMDA受体的变化与作用,本实验通过建立慢性不可预见性温和应激(CUMS)抑郁模型,并采用微量注射的方式向不同组大鼠的NAc区注射NMDA受体的激动剂NMDA及抑制剂MK-801,检测各组大鼠间行为差异。使用高效液相色谱(HLPC)、免疫印迹方法(Western blot, WB)分别检测大鼠NAc中谷氨酸、NMDA受体NR2B亚基、多巴胺D2受体等分子的在NAc中的变化。实验结果如下：1.与正常对照组相比,CUMS大鼠表现出明显的快感缺失,探究减少等抑郁样行为。同时,伴随NAc中谷氨酸的水平极显著增加。NR2B亚基的表达水平未发生显著变化。2.与CUMS组大鼠相比较,向正常大鼠NAc区注射MK-801并不影响动物行为。3.NAc微量注射MK-801能改善由CUMS引起的抑郁样行为,并且会使NAc中谷氨酸的水平显著降低,达到正常组大鼠水平,且NR2B表达也下降。4. NMDA能够诱导正常大鼠表现出抑郁样行为,且NAc中谷氨酸浓度升高。5.在应激或注射NMDA、MK-801对多巴胺D2受体表达均无显著影响。实验结果表明,NAc中谷氨酸及其NMDA受体参与了抑郁样行为的发生。其机制主要是应激导致的NMDA受体过度激活。NMDA受体激活对NAc中的谷氨酸浓度具有正反馈调节的作用。正是因为这种相互作用使得NAc中谷氨酸能系统失调,最终导致抑郁样行为发生。谷氨酸及其NMDA受体可能并不参与对多巴胺D2受体表达的调节。
[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.
【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.4
本文编号：2122572
[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.
【学位授予单位】：陕西师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.4
【参考文献】
相关期刊论文 前1条
1 朱熊兆;彭素芳;马秀玲;李婷;;母爱剥夺对成年大鼠情绪及多巴胺转运蛋白基因表达的影响[J];中南大学学报(医学版);2010年01期
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