髓样分化因子88参与突触功能调控的电生理研究

发布时间：2018-11-24 13:21

【摘要】：癫痫是由不同病因引起的脑部神经元高度同步化,以发作性、短暂性、重复性及刻板性的中枢神经系统功能失常为特征的临床综合症。Toll样受体(Toll-like receptor, TLR)是一组在天然免疫系统中起关键作用的模式识别受体(pattern recognition receptor; PRR),在天然免疫反应中具有重要作用。髓样分化因子88(myeloid differentiation primary response gene88, MyD88)是最早募集到Toll样受体的关键分子。已有研究表明TLR/MyD88介导的炎症反应与脑损伤引发的癫痫及一些神经退行性疾病密切相关。但是MyD88在中枢神经系统中的作用却鲜有研究。 MyD88在中枢神经系统(central nervous system, CNS)发育过程中持续地高表达,特别是海马区,提示MyD88可能具有参与免疫反应外的其它功能。因此,我们利用MyD88的全敲小鼠,研究MyD88及其信号通路在中枢神经系统突触发育过程中作用。我们通过电生理实验证明：MyD88全敲小鼠海马Schaffer侧枝-CAl锥体细胞间兴奋性突触传递显著增强,而抑制性突触传递没有明显变化。兴奋与抑制的不平衡导致MyD88全敲小鼠更易被红藻酸(Kainic acid,KA)诱发癫痫,提示MyD88及其介导的通路可能起平衡兴奋性突触功能的作用。
[Abstract]:Epilepsy is a clinical syndrome characterized by paroxysmal, transient, repetitive, and stereotypical central nervous system dysfunction characterized by high synchronization of brain neurons caused by different etiology. Toll like receptor (Toll-like receptor,) TLR) is a group of pattern recognition receptors (pattern recognition receptor;) that play a key role in the innate immune system. PRR), plays an important role in innate immune response. Myeloid differentiation factor 88 (myeloid differentiation primary response gene88, MyD88 is the first key molecule to recruit Toll like receptor. It has been shown that TLR/MyD88 mediated inflammation is closely related to brain injury induced epilepsy and some neurodegenerative diseases. However, the role of MyD88 in the central nervous system is rarely studied. The overexpression of MyD88 during the development of (central nervous system, CNS) in the central nervous system, especially in the hippocampal area, suggests that MyD88 may be involved in other functions other than immune response. Therefore, we used MyD88 knockout mice to study the role of MyD88 and its signaling pathway in the synaptic development of the central nervous system. Our electrophysiological experiments showed that the excitatory synaptic transmission between CAl pyramidal cells and Schaffer lateral branches in the hippocampus of MyD88 knockout mice was significantly enhanced, but the inhibitory synaptic transmission did not change significantly. The imbalance between excitation and inhibition makes MyD88 mice more susceptible to kainic acid (Kainic acid,KA) induced epilepsy, suggesting that MyD88 and its mediated pathway may play a role in balancing excitatory synaptic function.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1

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