發(fā)布時(shí)間：2018-04-26 03:26

  本文選題：初級(jí)纖毛 + 纖毛病��； 參考：《華東師范大學(xué)》2017年碩士論文

【摘要】：初級(jí)纖毛(primary cilia)是生長(zhǎng)于細(xì)胞表面的絲狀結(jié)構(gòu),廣泛存在于生物體的多種細(xì)胞中。長(zhǎng)期以來(lái)初級(jí)纖毛一直被認(rèn)為只是聽(tīng)覺(jué)、視覺(jué)等感受細(xì)胞的刺激信號(hào)轉(zhuǎn)導(dǎo)"器官"。在早期發(fā)育過(guò)程中,神經(jīng)干細(xì)胞上的初級(jí)纖毛被發(fā)現(xiàn)具有傳導(dǎo)Shh、Wnt等重要形態(tài)發(fā)生素的胞內(nèi)信號(hào)的功能。除此之外,初級(jí)纖毛對(duì)細(xì)胞有何影響并不清楚。直到近年多項(xiàng)重要的相關(guān)研究的發(fā)表,初級(jí)纖毛之于細(xì)胞的其他生理功能才逐漸引起人們的關(guān)注。初級(jí)纖毛的異常會(huì)引起一類稱為"纖毛病"的綜合癥,這類疾病涉及人體各個(gè)器官組織的多種臨床表現(xiàn)。盡管已經(jīng)鑒別了超過(guò)50種引起纖毛病的基因,但器官組織如何發(fā)生病變的相關(guān)信號(hào)通路、病理原理仍不是很明確。小清蛋白陽(yáng)性中間神經(jīng)元(parvalbumin positive interneuron)是腦內(nèi)一類重要的中間神經(jīng)元,其功能異常與多種精神性疾病的病理機(jī)制密切相關(guān)。本實(shí)驗(yàn)通過(guò)Cre-LoxP重組酶系統(tǒng)對(duì)C57/BL6小鼠小清蛋白陽(yáng)性神經(jīng)元上的初級(jí)纖毛進(jìn)行敲除,從而研究初級(jí)纖毛在小清蛋白陽(yáng)性神經(jīng)元所發(fā)揮的作用及對(duì)小鼠行為表型的影響。1)以小清蛋白陽(yáng)性神經(jīng)元上初級(jí)纖毛被敲除的成年小鼠(PV-Cre::Ift88flox)為研究對(duì)象,通過(guò)免疫熒光染色的方法觀察到小清蛋白陽(yáng)性神經(jīng)元主要分布于皮層、紋狀體、海馬、外部皮層下丘及小腦,且其上的初級(jí)纖毛顯著減少。2)以小清蛋白陽(yáng)性神經(jīng)元上初級(jí)纖毛被敲除的成年小鼠為研究對(duì)象,通過(guò)曠場(chǎng)試驗(yàn)、高架O迷宮實(shí)驗(yàn)、強(qiáng)迫游泳實(shí)驗(yàn)、前脈沖抑制實(shí)驗(yàn)、轉(zhuǎn)棒實(shí)驗(yàn)等行為學(xué)檢測(cè)手段評(píng)估小鼠的各類行為表型。實(shí)驗(yàn)結(jié)果顯示敲除初級(jí)纖毛的小鼠的行為表型存在性別差異,但總體表現(xiàn)趨勢(shì)一致,表現(xiàn)為自發(fā)活動(dòng)量升高,焦慮程度降低�？偟膩�(lái)說(shuō),在小鼠小清蛋白陽(yáng)性神經(jīng)元上敲除初級(jí)纖毛并未對(duì)小鼠的表型產(chǎn)生廣泛的影響,但其情緒明顯受到了影響,基于目前的研究及其他文獻(xiàn)的報(bào)道,推測(cè)是由于分布在前額葉皮層(prefrontal cortex)、紋狀體(striatum)等前腦部位的小清蛋白陽(yáng)性中間神經(jīng)元的功能受到影響而導(dǎo)致的,進(jìn)一步的影響機(jī)制仍有待深入探討。
[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.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：Q42

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 徐蕾;張雪寒;;多巴胺D1、D2受體在大鼠前扣帶皮層鈣結(jié)合蛋白陽(yáng)性中間神經(jīng)元的分布（英文）[J];生理學(xué)報(bào);2015年02期

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本文編號(hào)：1804296