抑郁症前额叶皮层神经元结构和功能不协调的病理机制研究

发布时间：2018-12-11 15:50

【摘要】：背景：抑郁症是一种以长时间情绪低落、兴趣和快感缺失、自我评估低下为特征的情绪性疾病。慢性应激作用于遗传易感个体可能导致单胺类递质系统和下丘脑-垂体-肾上腺轴的功能的损伤,这些致病因素进而导致边缘系统神经元萎缩与功能衰退,以及抑郁症的发生。但是,细胞类型特异性的发病机制仍然不清楚。因此我们研究了在抑郁症发病过程中前额叶皮层GABA能神经元与谷氨酸能神经元之间相互作用的病理变化。方法：利用疾病动物模型和转基因动物可以有效地帮助我们研究一些人类疾病的发病机理。给予小鼠长达3周的慢性不可预测的温和应激处理之后,经过糖水偏嗜、Y迷宫和强迫游泳等测试鉴定其表现出了抑郁样行为。对这些抑郁样行为组小鼠和对照组小鼠,我们通过利用细胞成像和电生理等技术研究了其内侧前额叶皮层脑区GABA能神经元和谷氨酸能神经元的结构和功能的变化。结果：与对照组相比,抑郁样行为组小鼠的前额叶皮层GABA能神经元的细胞亚结构功能不协调,表现为细胞兴奋性低下和突触输出减弱,而接收来自兴奋性的信息输入却是增加的。另外,谷氨酸能神经元接收到的来自GABA能神经元的突触前输入是减弱的,但其突触后反应却是增强的,而自身的兴奋性并未发生变化。结论：慢性不可预测的温和应激能够诱导小鼠表现出抑郁样行为。其诱导的前额叶皮层神经元细胞亚结构的功能不协调以及不同类神经元之间相互作用的失衡可能是抑郁症的病理基础。平衡细胞各部分的功能协调可能是治疗该类神经疾病的一个理想切入点。
[Abstract]:Background: depression is an emotional disorder characterized by prolonged depression, lack of interest and pleasure, and low self-assessment. Chronic stress may lead to damage of monoamine transmitter system and hypothalamus-pituitary-adrenal axis, which in turn lead to atrophy and decline of neurons in the limbic system, as well as depression. However, the pathogenesis of cell type specificity remains unclear. So we studied the pathological changes of the interaction between GABA neurons and glutamate neurons in prefrontal cortex during depression. Methods: using animal models of disease and transgenic animals can effectively help us to study the pathogenesis of some human diseases. After being treated with chronic unpredictable mild stress for up to 3 weeks, the mice showed depressive behavior after sucrose preference, Y maze and forced swimming tests. The changes of structure and function of GABA and glutaminergic neurons in medial prefrontal cortex were studied by cell imaging and electrophysiology in these depressive and control mice. Results: compared with the control group, the substructure of GABA neurons in the prefrontal cortex of the depressive behavior group was not coordinated, showing that the excitability of the cells was low and the synaptic output was decreased. And receiving information input from the excitability is increased. In addition, the presynaptic inputs from GABA neurons received by glutaminergic neurons were attenuated, but their postsynaptic responses were enhanced, while their excitability did not change. Conclusion: chronic unpredictable mild stress can induce depressive behavior in mice. The uncoordinated substructure of neurons in the prefrontal cortex and the imbalance of the interaction between different neurons may be the pathological basis of depression. Balancing the functional coordination of the various parts of the cell may be an ideal entry point for the treatment of these neurological diseases.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R749.4

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