糖皮质激素对杏仁核GABA能和谷氨酸能神经元功能的影响及其机制研究

发布时间：2018-06-25 19:00

本文选题：糖皮质激素 + 抑郁症　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:探讨糖皮质激素是如何影响杏仁核亚细胞结构及兴奋性神经元和抑制性神经元之间的相互作用的影响及其机制,或许能够揭示制度抑郁症及焦虑的病理机制。方法:地塞米松对于神经元的作用是通过把地塞米松急性洗在杏仁核脑片上或者直接给小鼠腹腔注射两种方式进行探讨。用700B放大器在电压钳下记录突触兴奋性,在电流钳下记录细胞细胞自身特性。GABA能神经元的功能的研究通过记录自身兴奋性以及抑制性输出来表示,谷氨酸能神经元功能的研究通过记录自身兴奋性及兴奋性输出来表示,杏仁核神经元动作电位发放能力通过注入去极化电流来研究。以谷氨酸能神经元被黄色荧光蛋白标记、GABA能神经元被绿色荧光蛋白标记的转基因小鼠的杏仁核为研究对象,通过一天一次慢性注射(40mg/kg)一周地塞米松及地塞米松(25μM)急性洗在脑片上两种方式,运用全细胞膜片钳,通过记录在谷氨酸能神经元记录自发抑制性突触后电位(spontaneous inhibitory postsynaptic current,s IPSC)、动作电位时间间隔(inter spike intervals,ISI)及在GABA能神经元记录自发兴奋性突触后电位(spontaneous excitatory postsynaptic current,s EPSC)、动作电位时间间隔(inter spike intervals,ISI)反应神经元的动作电位和突触传递,探讨糖皮质激素对于杏仁核亚细胞结构和神经元相互作用网络的影响。结果:慢性应用地塞米松增加抑制性神经元GABA能神经递质的释放,并且增加兴奋性神经元上GABAA受体的反应性。急性应用地塞米松能够增加抑制性神经元GABA神经递质的释放,对GABAA受体反应性没有明显影响。急性和慢性应用地塞米松都能增加GABA能神经元动作电位的发放能力,增加细胞自身兴奋性。慢性应用地塞米松能够下调兴奋性神经元释放谷氨酸能神经递质,并且急性应用地塞米松也能下调兴奋性神经元谷氨酸能神经递质的释放。急性和慢性应用地塞米松对谷氨酸能神经元动作电位发放能力没有明显影响。应用地塞米松对于杏仁核抑制性神经元和兴奋性神经元产生不同的作用,急性和慢性应用地塞米松都会上调GABA能神经元的递质释放和动作电位发放能力以及下调谷氨酸能的递质释放,慢性应用地塞米松也会增加GABA受体的反应性。结论:地塞米松通过提高突触前神经元活性、GABA能神经元的释放以及突触后GABAA受体的反应性上调GABA能神经元对于谷氨酸能神经元的作用;通过降低谷氨酸能神经递质的释放降低谷氨酸能神经元对于GABA能神经元的作用。杏仁核谷氨酸能神经元功能的下调与GABA能神经元的上调与损伤了神经网络的平衡,这种对于处于抑制状态的杏仁核神经网络调节的不协调或许导致应激状态的情绪情感障碍,为抗抑郁药物开发提供新思路。
[Abstract]:Objective: To explore the effect of glucocorticoid on the interaction between the amygdala subcellular structure and the interaction between excitatory and inhibitory neurons, and perhaps to reveal the pathological mechanism of institutional depression and anxiety. Methods: Dexamethasone's effect on neurons is through the acute washing of dexamethasone in the amygdala. Two ways of intraperitoneal injection were conducted on or directly to the mice. 700B amplifier was used to record synaptic excitability under voltage forceps, and the function of cell cell itself characteristic.GABA neurons under current forceps was recorded by recording self excitability and suppressive transmission, and the function of glutamic acid neurons was studied. The action potential delivery ability of amygdala neurons was studied by injection depolarization current. The glutamic acid neurons were labeled with yellowish fluorescent protein. The apricot kernel of transgenic mice marked by green fluorescent protein (GABA) neurons was studied by a single day chronic injection. An acute wash of dexamethasone (40mg/kg) and dexamethasone (25 mu M) on the brain slices in two ways, using the whole cell patch clamp, recording the spontaneous inhibitory postsynaptic potential (spontaneous inhibitory postsynaptic current, s IPSC) by recording the glutamic acid neurons, the time interval of the action potential (inter spike intervals, ISI) and The neurons recorded the spontaneous excitatory postsynaptic potential (spontaneous excitatory postsynaptic current, s EPSC), the action potential and synaptic transmission of the action potential time interval (inter spike intervals, ISI), and the effects of glucocorticoid on the structure of the amygdala subcell and the neural interaction network. Dexamethasone increases the release of GABA neurotransmitters in inhibitory neurons and increases the responsiveness of GABAA receptors on excitatory neurons. Acute dexamethasone can increase the release of GABA neurotransmitters in the inhibitory neurons and have no significant response to the responsiveness of the GABAA receptor. Both acute and chronic use of dexamethasone can increase G ABA can increase the ability of neuronal action potential to increase cell self excitability. Chronic dexamethasone can reduce the release of glutamatergic neurotransmitters from excitatory neurons, and acute dexamethasone can also reduce the release of glutamate neurotransmitters in excitatory neurons. Acute and chronic dexamethasone is capable of glutamatergic neurotransmitters The use of dexamethasone has different effects on the amygdala and the excitatory neurons in the amygdala. The acute and chronic use of dexamethasone can up-regulate the release of GABA neurons and the ability to release the action potential and reduce the release of glutamate neurotransmitters. Dexamethasone also increases the reactivity of GABA receptors. Conclusion: dexamethasone can increase the action of GABA neurons to glutamic neurons by increasing the activity of pre synapse neurons, release of GABA energy neurons and the reactivity of postsynaptic GABAA receptors, and reduce glutamatergic neurotransmitters to reduce glutamatergic neurons by reducing the release of glutamate neurotransmitters. The downregulation of the function of glutamic neurons in the amygdala and the up-regulation of the GABA energy neurons and the balance of the neural network, the incoordination of the regulation of the amygdala neural network in the state of inhibition may lead to emotional and emotional disorders in the state of stress and provide new ideas for the development of antidepressant drugs in the amygdala.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.4

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