下丘脑外侧区（LH）和杏仁核前区（AA）神经免疫调节相关信号研究

发布时间：2018-02-12 06:35

本文关键词： 神经免疫调节神经元凋亡下丘脑外侧区杏仁核前区突触可塑性　出处：《中国协和医科大学》2008年硕士论文　论文类型：学位论文

【摘要】： 神经内分泌-免疫网络学说是神经免疫学科的基础理论,建立神经内分泌-免疫调节网络的解剖学构筑是神经免疫学、神经解剖学、神经生理学和神经内分泌学多学科协作研究的中心任务。本论文实验研究的核心是探讨LH、AA脑区参与神经免疫调节功能相关的信号和信号传导模式。在课题组前期工作的基础上,我们应用基因芯片技术检测分析大鼠LH、AA脑区神经免疫调节功能相关的信号,进一步应用PathWay Miner公共数据库对功能相关基因及其编码蛋白的分子功能、组织分布、细胞内定位、表达水平的影响因素和信号传导树等特性进行比对分析,探索该脑区参与神经免疫调节的信号和信号传导通路,为进一步阐明神经免疫调节网络的解剖学构筑提供实验依据。与正常对照组基因表达谱比较,实验组大鼠LH、AA脑区共有530个差异表达基因与免疫调节功能相关:2天组共有399个基因差异表达,4天组共有78个基因差异表达,6天组共有196个基因差异表达;其中已知功能基因共275个。这些差异表达基因编码蛋白包括膜受体、神经介质、蛋白激酶/磷酸酶、小分子GTP酶超家族、细胞骨架及其相关蛋白、转录因子等多种信号分子。这些信号分子在信号传导树中的位置和相互联系表明上述差异基因的活化表达启动了诱导递质合成释放、突触重塑、凋亡调控、神经元再生等神经细胞生理功能活动相关的多条信号传导通路。我们的研究证明LH、AA脑区神经免疫调节功能相关的神经元功能活动模式为:1)已合成的神经递质释放;2)启动功能相关基因的转录和表达,合成神经免疫调节功能相关的信号物质;3)通过诱导功能活动的神经元凋亡和突触重塑、神经前体细胞的增殖分化,实现神经免疫调节功能下调和网络构筑重建;4)合成激素、神经肽等神经内分泌免疫调节信号,通过下丘脑.垂体-肾上腺轴通路参与免疫系统功能调控。神经免疫调节功能是一个复杂的生理功能调节过程,多信号、多通路、以及多种调节方式的存在符合神经生理功能调节网络活动的基本模式。LH和AA脑区参与神经免疫调节功能活动的神经元通过细胞凋亡方式下调网络功能活动有悖于经典的神经生理功能活动模式,是神经免疫调节功能相关脑区神经元独有的应答模式,其生物学意义是维持了神经免疫调节功能的免疫事件的特异性。
[Abstract]:The theory of neuroendocrine immune network is the basic theory of neuroimmunity, and the anatomical construction of neuroendocrine immune regulatory network is neuroimmunology, neuroanatomy, neuroimmunology, neuroimmunology, neuroimmunology, neuroimmunology and neuroanatomy. The core of this paper is to explore the signal and signal transduction patterns of LHAA brain area involved in neuroimmunomodulation function. Based on the previous work of the research group, the main task of this paper is to study the neurophysiology and neuroendocrinology. We used the gene chip technique to detect and analyze the signals related to the neuroimmunomodulation function in the brain region of rat LHH AA, and further applied the PathWay Miner common database to the molecular function, tissue distribution and intracellular localization of the function-related genes and their encoded proteins. The influencing factors of expression level and the characteristics of signal transduction tree were compared and analyzed to explore the signal and signal transduction pathway in the brain region involved in neuroimmune regulation, and to provide experimental basis for further elucidating the anatomical construction of neural immune regulatory network. Gene expression profile was compared with that of normal control group. There were 530 differentially expressed genes in the brain region of the experimental group. There were 399 differentially expressed genes and 196 differentially expressed genes in the 6-day group. These differentially expressed genes include membrane receptors, neurotransmitters, protein kinase / phosphatase, small molecular GTP superfamily, cytoskeleton and related proteins. Transcription factors and other signal molecules. The location and interrelation of these signaling molecules in the signal transduction tree indicate that the activation and expression of these differentially expressed genes initiate the induction of transmitter synthesis and release, synaptic remodeling, apoptosis regulation, Multiple signal transduction pathways associated with physiological functional activities of neurons, such as neuronal regeneration. Our study has demonstrated that the neuronal functional activity related to neuroimmunomodulation in the LHHAA brain region is the release of synthesized neurotransmitters in the form of 1: 1). 2) transcription and expression of genes related to the initiation of function, By inducing neuronal apoptosis and synaptic remodeling, proliferation and differentiation of neural precursor cells, down-regulation of neural immunomodulation function and reconstruction of network architecture are realized. Neuroendocrine and immunomodulatory signals, such as neuropeptides, participate in the regulation of immune system function through hypothalamus and pituitary-adrenal axis pathway. Neuroimmune regulatory function is a complex physiological function regulation process, multi-signal, multi-pathway, And the existence of many regulation modes accord with the basic mode of neurophysiological function regulating network activity. The neurons in the brain area of LH and AA that participate in the neuronal immunomodulatory function activity down-regulate the network function through the way of apoptosis. Classic neurophysiological activity patterns, It is a unique response mode of neurons related to neuroimmune regulatory function in the brain, and its biological significance is to maintain the specificity of immune events that regulate neuroimmune function.
【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R392

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