NMDA受体与中枢神经系统发育

中枢神经系统兴奋性氨基酸离子型受体－ＮＭＤＡ受体,是由ＮＭＤＡＲ１和ＮＭＤＡＲ２两个亚单位共同构成的受体通道复合体。ＮＭＤＡ受本激活后可引起神经元细胞对Ｎａ＾＋,Ｋ＾＋和Ｃａ＾２＋通透性增强,产生兴奋性突触后电位,在中枢神经发育的过程中,ＮＭＤＡ受体通过不同亚型的选择性表达,改变自身的结构和功能,进而影响ＮＭＤＡ受体介导的Ｃａ＾２＋内流,调节神经元内Ｃａ＾２＋依赖的第二信使系统,最终实现对中枢神经     

DNA甲基化在中枢神经系统发育中的研究进展

DNA甲基化是最早被发现的表观遗传修饰之一。近年来,大量的研究显示DNA甲基化在中枢神经系统(CNS)发育中发挥了重要作用。不同种类的DNA甲基转移酶(Dnmt)和DNA甲基结合蛋白(MBD)在CNS发育的不同阶段发挥不同的作用。DNA甲基化促进神经干细胞向神经元方向分化,抑制其向胶质细胞分化。Dnmt和MBD主要在神经元中表达,而在胶质细胞不表达或表达较少。DNA甲基化调节神经发生和突触的形成,参与学习记忆。星型胶质细胞的标志物GFAP去甲基化促进早期神经上皮分化为星型胶质细胞。少突胶质细胞相关基因MAG和Sox10等也受甲基化的调节。本文主要从以上方面综述了DNA甲基化在中枢神经系统发育中的作用。     

NMDA受体与中枢神经系统的发育

离子型谷氨酸受体分为NMDA型和非NMDA型两类,其中NMDA型受体与中枢神经系统发育关系密切。本文综述了NMDA受体的分子特性及NMDA受体五种亚单位NR1、NR2A、NR2B、NR2C和NR2D在动物出生后脑内的时空表达;NMDA受体亚单位在发育中的作用以及NMDA受体活性的胞内调节机制。     

GABA在中枢神经系统发育的早期阶段具有兴奋作用

在发育早期中枢神经系统γ－氨基丁酸（γ-aminobutyric acid,GABA）主要作为兴奋性神经递质而发挥作用,它可使神经元产生去极化,升高胞内Ca^2 浓度,此时GABA发挥了重要的神经营养性作用,随着兴奋性谷氨酸能系统的发育,通过Cl^-转运体的表达变化,胞内Cl^-浓度降低,从而使GABA由兴奋性转变为抑制性。     

巢蛋白mRNA在小鼠中枢神经系统发育过程中的表达

巢蛋白属于中等纤维基因家族,在增殖较快的神经前体细胞中表达。该基因被克隆后,作为神经前体的标记基因得到广泛应用。本文中,我们根据小鼠巢蛋白ｃＤＮＡ序列,设计了一对引物,在确定了反轩录ＰＣＲ反应的最佳反应条件后,详细地考察了小鼠巢蛋白ｍＲＮＡ在中枢神经系统发育过程中的表达规律。     

先天性CMV感染致中枢神经系统畸形发育机制

胎儿中枢神经系统(central nervous system,CNS)是人类巨细胞病毒(human cytomegalovirus,HCMV)先天性感染的主要靶器官。胚胎期CMV感染常常导致严重CNS畸形的发生,其前提条件是CNS中的神经前体(干)细胞、神经元及神经胶质细胞对CMV普遍易感。发育期CNS感染CMV具有以下特点:⑴神经系统细胞对CMV的容纳性在CNS的不同发育阶段有所不同;⑵受累的细胞数随着发育的进展而增多;⑶CNS不同部位的细胞对CMV的敏感性存在明显的差异;⑷感染发生时细胞所处细胞周期的时相也与感染严重程度密切相关。CMV感染能诱导宿主细胞特异性的染色体折断,影响Homeobox基因(胚胎发育的主控基因)的表达,进而阻断细胞周期(G1期滞留)、诱导细胞凋亡,导致CNS细胞数量减少与迁徙异常,最终导致C N S发育畸形。     

肾上腺素受体在大鼠中枢神经系统发育中的作用研究

去甲肾上腺素和肾上腺素受体在大鼠中枢神经系统（CNS）的发育早期开始表达,且受体表达的时空模式与脑发育过程中某些脑区神经元的迁移和分化相一致,这提示去甲肾上腺素在中枢神经系统的发育中具有重要作用。本文论述了胚胎和新出生的大鼠不同脑区肾上腺素受体mRNA的表达模式以及这些受体对体外培养的成熟细胞和相应的前体细胞的调控效应,通过离体和在体研究的实验证据,阐述肾上腺素受体介导了去甲肾上腺素对神经前体细胞的增殖、生长、迁移、分化和存活的调控作用。进一步明确了去甲肾上腺素在CNS发育中所起的作用,使其可作为成体脑修复的助动剂而赋予新的意义。     

峡视核——研究中枢神经系统发育及细胞凋亡的新模型

鸟类离中系统的峡视核是近年来研究中枢神经系统发育过程中细胞凋亡的新模型.在其发育过程中,随着核团的形成、折叠及分层,伴有一些与峡视核相关的临时神经通路的形成和消失,与此同时,该核团中神经元有一半以上发生细胞凋亡.研究表明,形成正确的传入和传出联系对神经元的存活十分重要.分子水平上的机制研究揭示,细胞凋亡与一系列神经营养因子及其相应的受体相关.细胞凋亡对中枢神经系统发育过程中正确神经通路的形成有重要意义.     

N6-甲基化腺嘌呤RNA甲基化修饰在中枢神经系统中的作用研究进展

mRNA存在多种转录后修饰,这些修饰调控mRNA的稳定和剪接、翻译、转运等多个过程,进而影响细胞发育、机体免疫、学习认知等重要生理功能。其中m⁶A修饰是转录后修饰中最丰富的一种,广泛存在于mRNA中,调控mRNA的代谢活动,影响基因表达。m⁶A修饰的稳态对神经系统的发育和功能维持至关重要。近年研究发现,在神经退行性疾病、精神疾病和脑肿瘤中均存在m⁶A修饰的身影。因此本文对近几年m⁶A甲基化修饰在中枢神经系统发育、功能及相关疾病中的作用进行总结,为神经系统疾病提供潜在的临床治疗靶点。     

Histamine metabolism and its role in central nervous system function

The present day data concerning biosynthesis, storage, release and inactivation of histamine in the brain of mammals are given. The possibility to regulate histamine of the action of physiologically active substances is discussed.     

Disinhibition and its role in central nervous system activity]

The review concerning neuronal mechanisms of disinhibition and its participation in activities of the spinal cord, cerebellum, reticulo-thalamo-cortical system, basal ganglia and cerebral cortex is presented.     

The role of GSK3beta in the development of the central nervous system

Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine kinase.It is particularly abundant in the developing central nervous system (CNS).Since GSK3β has diverse substrates ranging fr...     

The role of astrocyte-secreted matricellular proteins in central nervous system development and function

Matricellular proteins, such as thrombospondins (TSPs1-4), SPARC, SPARC-like1 (hevin) and tenascin C are expressed by astrocytes in the central nervous system (CNS) of rodents. The spatial and temporal expression patterns of these proteins suggest that they may be involved in important developmental processes such as cell proliferation and maturation, cell migration, axonal guidance and synapse formation. In addition, upon injury to the nervous system the expression of these proteins is upregulated, suggesting that they play a role in tissue remodeling and repair in the adult CNS. The genes encoding these proteins have been disrupted in mice. Interestingly, none of these proteins are required for survival, and furthermore, there are no evident abnormalities at the gross anatomical level in the CNS. However, detailed analyses of some of these mice in the recent years have revealed interesting CNS phenotypes. Here we will review the expression of these proteins in the CNS. We will discuss a newly described function for thrombospondins in synapse formation in the CNS in detail, and speculate whether other matricellular proteins could play similar roles in nervous system development and function.     

Tenascin-R: role in the central nervous system

Tenascin-R (TN-R), a member of the tenascin family of extracellular matrix glycoproteins, is exclusive to the nervous system. It affects cell migration, adhesion and differentiation, although no remarkable clinical consequences have been shown in knock-out animal models. TN-R's expression pattern suggests a possible primary or secondary role in certain neurological problems including malformations, tumors and neurodegenerative disorders. This review summarizes the structure and molecular interactions of this molecule and discusses its function and possible roles in the central nervous system.     

阿片类物质在中枢神经系统的免疫调控作用

内源及外源性阿片具有调节神经元与胶质细胞的功能,这些调节具有保护或损伤脑功能的双重作用。吗啡具有促进受病毒复制及继发感染的作用。另一方面,阿片受体中的ｋａｐｐａ受体可能具有保护神经元的作用。更深层次的研究应是了解阿片通过什么机制作用在胶质细胞和神经元上,藉此以促进研制出具有明显疗效的新药。     

The role of agrin in synaptic development,plasticity and signaling in the central nervous system

Development of the neuromuscular junction (NMJ) requires secretion of specific isoforms of the proteoglycan agrin by motor neurons. Secreted agrin is widely expressed in the basal lamina of various tissues, whereas a transmembrane form is highly expressed in the brain. Expression in the brain is greatest during the period of synaptogenesis, but remains high in regions of the adult brain that show extensive synaptic plasticity. The well-established role of agrin in NMJ development and its presence in the brain elicited investigations of its possible role in synaptogenesis in the brain. Initial studies on the embryonic brain and neuronal cultures of agrin-null mice did not reveal any defects in synaptogenesis. However, subsequent studies in culture demonstrated inhibition of synaptogenesis by agrin antisense oligonucleotides or agrin siRNA. More recently, a substantial loss of excitatory synapses was found in the brains of transgenic adult mice that lacked agrin expression everywhere but in motor neurons. The mechanisms by which agrin influences synapse formation, maintenance and plasticity may include enhancement of excitatory synaptic signaling, activation of the “muscle-specific” receptor tyrosine kinase (MuSK) and positive regulation of dendritic filopodia. In this article I will review the evidence that agrin regulates synapse development, plasticity and signaling in the brain and discuss the evidence for the proposed mechanisms.