初级纤毛在中间神经元上所起作用的初步研究

发布时间：2018-04-26 03:26

本文选题：初级纤毛 + 纤毛病　；参考：《华东师范大学》2017年硕士论文

【摘要】：初级纤毛(primary cilia)是生长于细胞表面的丝状结构,广泛存在于生物体的多种细胞中。长期以来初级纤毛一直被认为只是听觉、视觉等感受细胞的刺激信号转导"器官"。在早期发育过程中,神经干细胞上的初级纤毛被发现具有传导Shh、Wnt等重要形态发生素的胞内信号的功能。除此之外,初级纤毛对细胞有何影响并不清楚。直到近年多项重要的相关研究的发表,初级纤毛之于细胞的其他生理功能才逐渐引起人们的关注。初级纤毛的异常会引起一类称为"纤毛病"的综合症,这类疾病涉及人体各个器官组织的多种临床表现。尽管已经鉴别了超过50种引起纤毛病的基因,但器官组织如何发生病变的相关信号通路、病理原理仍不是很明确。小清蛋白阳性中间神经元(parvalbumin positive interneuron)是脑内一类重要的中间神经元,其功能异常与多种精神性疾病的病理机制密切相关。本实验通过Cre-LoxP重组酶系统对C57/BL6小鼠小清蛋白阳性神经元上的初级纤毛进行敲除,从而研究初级纤毛在小清蛋白阳性神经元所发挥的作用及对小鼠行为表型的影响。1)以小清蛋白阳性神经元上初级纤毛被敲除的成年小鼠(PV-Cre::Ift88flox)为研究对象,通过免疫荧光染色的方法观察到小清蛋白阳性神经元主要分布于皮层、纹状体、海马、外部皮层下丘及小脑,且其上的初级纤毛显著减少。2)以小清蛋白阳性神经元上初级纤毛被敲除的成年小鼠为研究对象,通过旷场试验、高架O迷宫实验、强迫游泳实验、前脉冲抑制实验、转棒实验等行为学检测手段评估小鼠的各类行为表型。实验结果显示敲除初级纤毛的小鼠的行为表型存在性别差异,但总体表现趋势一致,表现为自发活动量升高,焦虑程度降低。总的来说,在小鼠小清蛋白阳性神经元上敲除初级纤毛并未对小鼠的表型产生广泛的影响,但其情绪明显受到了影响,基于目前的研究及其他文献的报道,推测是由于分布在前额叶皮层(prefrontal cortex)、纹状体(striatum)等前脑部位的小清蛋白阳性中间神经元的功能受到影响而导致的,进一步的影响机制仍有待深入探讨。
[Abstract]:Primary cilia (primary cilia) is a filamentous structure that grows on the surface of cells and widely exists in a variety of biological cells. Primary cilium has long been considered as an organ of stimulating signal transduction of auditory, visual and other sensory cells. During early development, the primary ciliates on neural stem cells were found to have the function of conducting intracellular signals of important morphogenetic factors such as Shhln Wnt and so on. In addition, the effect of primary cilia on cells is unclear. Until the publication of many important studies in recent years, the other physiological functions of primary ciliated cells have attracted more and more attention. Abnormalities in primary cilia can cause a class of syndromes called fibrous disorders, which involve a variety of clinical manifestations of various organs and tissues of the human body. Although more than 50 genes responsible for fiber defects have been identified, the pathophysiology of the signal pathways involved in the pathogenesis of organ lesions remains unclear. The parvalbumin positive interneuron is a kind of important interneuron in the brain. Its abnormal function is closely related to the pathological mechanism of many mental diseases. In this study, the primary ciliates of white albumin positive neurons in C57/BL6 mice were knocked out by Cre-LoxP recombinant enzyme system. In order to study the effect of primary cilia on the action of albumin positive neurons and its effect on the behavioral phenotype of mice, PV-Crew: 1) PV-Crew: I ft88 flox, which was knocked out of primary cilia, was used as the research object. By immunofluorescence staining, it was observed that the immunoreactive neurons were mainly distributed in cortex, striatum, hippocampus, inferior colliculus and cerebellum. And its primary cilia decreased significantly. 2) the adult mice whose primary cilia were knocked out from the whey protein positive neurons were studied by open field test, elevated O maze test, forced swimming test, pre pulse inhibition test. The behavioral phenotypes of mice were evaluated by behavioral methods such as rotation test. The results showed that there were gender differences in behavioral phenotypes of primary cilium knockout mice, but the overall performance trend was the same, showing increased spontaneous activity and decreased anxiety. Generally speaking, knockout of primary cilia from mouse whey protein positive neurons did not have a widespread effect on the phenotype of mice, but their mood was significantly affected, based on current studies and other literature reports. It is speculated that the function of the prefrontal cortex, striatum and other prefrontal cortex positive intermediate neurons is affected, and the mechanism of further influence remains to be further explored.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：Q42

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