小鼠海马CA1区轴棘突触相关特性的研究

发布时间：2018-01-18 15:40

本文关键词：小鼠海马CA1区轴棘突触相关特性的研究　出处：《河北医科大学》2006年博士论文　论文类型：学位论文

【摘要】： 在19世纪末,Ramon y Cajal首次提出典型树突棘由与树突相连的颈部和膨大的头部组成,并且提到这些位于众多神经元树突表面的微小突起是神经元之间相互作用的场所,认为树突棘形态的改变可能会引起神经元功能活动的变化。一个世纪以来,人们运用光镜和电镜技术证实,树突棘的确是突触信号输入的装置,在人类的大脑中含量超出1013,参与90%以上兴奋性突触的信息传递,是轴棘突触的重要结构。轴棘突触的树突棘头存在高电子密度的盘状结构,称为突触后致密体(PSD),镶嵌着许多重要的神经递/调质受体,在神经递/调质信号传递过程中起着重要作用。树突棘的数量或形态与突触的效能密切相关,当其发生改变时,暗示轴棘突触也出现了变化,因此,可以用指定区域内树突棘的密度与形态特征来表示此区域内突触的数量和状态。众所周知,海马CA1区与空间学习记忆密切相关,然而研究发现,学习记忆减退的衰老大鼠和小鼠齿状回颗粒细胞、海马CA1以及海马CA3区的锥体细胞并无神经元数目的减少,因此,衰老引起的学习记忆减退的形态基础很可能是神经元更微细的结构如轴棘突触的改变。脆性X综合症(FRX, fragile x syndrome)是常见的遗传性智力发育迟缓疾病,其发病率为男性1/4000,女性1/8000,仅次于Down’s综合症。这种疾病主要是由于FMR1基因5`末端CGG重复序列增加过多,导致其编码蛋白(FMRP)的表达缺乏。FRX小鼠模型是靶向破坏野生型小鼠的FMR1基因而建立,并具有其许多FRX患者的特征。FRX患者与FMR1基因敲除小鼠均表现有空间学习记忆障碍,暗示极有可能存在海马锥体细胞的树突棘和轴棘突触的形态异常。因此,我们通过研究正常小鼠、老年小鼠和FMR1基因敲除鼠海马CA1区轴棘突触的相关特性及其变化,为树突棘或轴棘突触参与衰老引起的学习记忆减退及FRX智力障碍提供神经解剖学依据。研究内容如下: 一、小鼠海马CA1区轴棘突触树突棘头与突触后致密体的相关性研究目的:树突棘与突触后致密体(PSD)是轴棘突触的重要结构,大的
[Abstract]:At the end of nineteenth Century, Ramon y Cajal first proposed the typical dendritic spines and dendrites connected by the neck and swollen head. At the end of the numerous small protrusions of neuronal dendrites is interaction between neurons where that dendritic spine morphology changes may lead to changes in the activity of neurons. For a century, people using light and electron microscopy confirmed that dendritic spines are device of synaptic input, in the human brain in excess of 1013, involved in more than 90% of excitatory synaptic transmission of information, is an important structure in axospinous synapses. There is disc structure with high electron density of dendritic spine head axospinous synapses, called synapses after the dense body (PSD), with many important neurotransmitters / neuromodulators receptors play an important role in neurotransmitter signaling process. And / or the number of dendritic spine morphology and synaptic Efficiency is closely related. When it changes, it implies that the axis spines synapse also changes. Therefore, the number and state of synapses in this area can be expressed by density and morphological characteristics of dendritic spines in designated areas.
As everyone knows, hippocampus CA1 region and spatial learning and memory are closely related, but the study found that the learning and memory of senile rats and mice granule cells in the dentate gyrus, hippocampus CA1 and CA3 region of the hippocampus pyramidal cells and no reduction in the number of neurons, therefore, learning and memory deficits caused by aging is likely to form the basis is more subtle structure of neurons if the axospinous synapses change.
Fragile X syndrome (FRX fragile, X syndrome) is a common inherited mental retardation disease, the incidence rate of male 1/4000, female 1/8000, after Down 's syndrome. This disease is mainly due to the FMR1 terminal of 5` gene CGG repeat sequence increases too much, leading to its coding protein (FMRP) expression of.FRX deficiency mouse model is targeting FMR1 gene disruption of wild-type mice and the establishment, features of.FRX patients with FMR1 gene and has many of its patients with FRX knockout mice showed spatial learning and memory disorders, suggesting that abnormal dendritic spines and axospinous synapses is likely to exist in hippocampal pyramidal cell morphology.
Therefore, we study the correlation properties in normal mice, hippocampal CA1 area axospinous synapses and changes in aged mice and FMR1 gene knock, providing neuroanatomical basis for learning and memory of dendritic spines or axospinous synapses involved in the aging caused by FRX impairment and mental retardation. The contents are as follows:
The study of the correlation between the synaptic dendrites of the synapse and the postsynaptic density in the hippocampal CA1 region of the hippocampus
Objective: dendritic spines and postsynaptic dense bodies (PSD) are important structures of axon synapses.

【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R322

【引证文献】