维生素D受体(VDR)对中枢神经系统功能作用的研究进展

维生素D是一种具有神经活性的类固醇激素,维生素D受体(vitamin D receptor,VDR)在胚胎期以及成年大脑组织的不同区域均有表达。越来越多的流行病学数据表明,VDR基因多态性以及维生素D缺乏与阿尔茨海默氏症、帕金森氏症等中枢神经系统疾病易感性有关。VDR对中枢神经系统可能具有重要作用。现综述VDR调控大脑发育以及神经保护作用的研究进展,以期为维生素D促进脑发育以及预防和治疗中枢神经系统疾病的应用提供理论参考。     

神经干细胞的研究现状及运用前景

近年来的研究表明胚胎期和成年期动物的神经组织及人脑中可以分离出神经干细胞.神经干细胞能不断增殖并且具有分化成神经元、星型胶质细胞和少突胶质细胞的能力.神经干细胞的这种特性为中枢神经系统退行性病变和损伤的治疗打下了基础.对神经干细胞的分布、生物学特性、鉴定、增殖与分化及其治疗中枢神经系统疾病中的应用前景进行了综述.     

Galanin(甘丙肽)及其受体在成年小鼠脑内神经新生部位的表达及对神经干细胞分化的作用

Galanin(甘丙肽)是一种在中枢神经系统中广泛分布的神经肽,功能涉及摄食、睡眠和觉醒、疼痛、认知和生殖等各方面.我们在成年小鼠脑的神经细胞新生部位如SVZ,DG和RMS发现有galanin及其受体的mRNA表达,同时在SVZ来源的神经干细胞中也检测到有galanin及其受体的表达.细胞实验中,在分化后特定时间段GALKO小鼠来源的神经干细胞产生神经突的细胞比例及神经突的长度明显小于正常小鼠来源的神经干细胞.而加入galanin或受体激动剂GAL2-11后.该神经干细胞则在产生神经突的细胞比例及神经突的长度都明显上升.受体拮抗剂M35的添加可减弱galanin或GAL2-11所产生的作用.这些结果表明galanin及其受体与神经干细胞的分化及神经突的生长有着密切的联系,并可能参与了神经系统的发育.     

OXR1基因的抗氧化作用及分子机制研究进展

抗氧化基因1 (oxidation resistance gene 1,OXR1)是一种仅存在于真核生物中,具有清除活性氧、防止细胞氧化损伤的抗氧化调节基因,近年来相关研究甚多.在哺乳动物中,OXR1高表达于中枢神经系统,对神经细胞的抗氧化保护起到至关重要的作用,并发现其功能在人类神经退行性疾病的靶向基因治疗中具有潜在...     

促红细胞生成素在低氧预适应中的神经保护作用

促红细胞生成素(EPO)是体内一种重要的糖蛋白激素,主要由胎肝和成人的肾脏产生。EPO的表达除受到转录因子的调控之外,还受到表观遗传学的调控。研究发现,EPO及其受体(EPOR)在中枢神经系统中广泛表达,提示其对中枢系统具有神经保护作用。低氧预适应是机体抗缺氧或缺血的一种内源性保护机制,它可以促进EPO表达,减轻低氧/缺血引起的神经元损伤。EPO主要通过激活一系列信号转导通路及多种可能的机制发挥神经保护作用。     

Nogo-A及其受体在中枢神经系统发育过程中作用及机制的研究进展

Nogo-A及其受体在成年哺乳动物的中枢神经系统(CNS)中,尤其是在中枢神经系统损伤及修复过程中的作用及机制已经被广泛而深入的研究,但是它们在CNS发育中的扮演的角色却了解甚少.新近研究表明,Nogo-A在CNS发育过程中神经前体细胞分化及迁移,轴突的生长及可塑性的变化以及少突胶质细胞前体细胞分化和成髓鞘化等过程中发挥着重要的作用.     

纳米银神经毒性研究进展

纳米银(sliver nanoparticles,AgNPs)性能优异,在肿瘤的早期诊断和神经系统疾病的诊治中应用广泛。然而纳米颗粒可经多种途径进入中枢神经系统,并可能在神经组织中蓄积,导致神经细胞功能紊乱和神经退行性病变。该综述阐述了纳米银的脑累积效应以及进入中枢神经系统的途径,主要包括嗅神经和血脑屏障途径;阐述了纳米银对中枢神经系统的影响和神经毒性作用机制,为进一步对纳米银的神经毒性作用机制研究及安全性评价提供参考依据。     

促红细胞生成素在脑缺血动物模型治疗中的研究进展

促红细胞生成素是一种促进红系造血前体细胞增殖、分化的细胞因子,主要作用为促进红细胞增殖,应用于临床各种贫血治疗。随着研究进展,学者发现促红细胞生成素为一种多功能营养因子及神经保护因子,具有调节中枢神经系统发育、神经营养及神经保护作用。脑缺血性卒中实验研究显示,促红细胞生成素可有效改善中枢神经系统疾病所致的神经功能缺损,本文主要概述促红细胞生成素在脑缺血性卒中动物模型的研究进展,及其发挥神经保护作用所经由的分子机制。相信随着实验研究进展,其在脑缺血性卒中临床治疗方面将拥有更广阔的前景。     

胃泌素释放肽受体在认知功能及行为中的作用

胃泌素释放肽(gastrin-releasing peptide,GRP)是哺乳动物体内的一种神经肽,它可以和细胞膜表面的胃泌素释放肽受体(gastrin-releasing peptide receptor,GRPR)结合产生相应生理作用。GRPR是G蛋白偶联受体超家族的成员,其介导的信号可以调节神经及神经内分泌方面的许多重要功能,包括认知功能和行为等方面。研究发现GRPR表达的改变可以引起神经退行性变、神经发育、心理紊乱等中枢神经系统疾病。GRPR在中枢神经系统疾病发生发展过程中有着重要作用,提示GRPR激动剂或者拮抗剂可能改善与神经疾病相关的认知和行为缺陷。     

Galanin（甘丙肽）及其受体在成年小鼠脑内神舭部位的表达及对神经干细胞分化的作用

Galallin（甘丙肽）是一种在中枢神经系统中广泛分布的神经肽,功能涉及摄食、睡眠和觉醒、疼痛、认知和生殖等各方面。我们在成年小鼠脑的神经细胞新生部位如SVZ,DG和RMS发现有galanin及其受体的mRNA表达,同时在SVZ来源的神经干细胞中也检测到有galanin及其受体的表达。细胞实验中．在分化后特定时间段GALKO小鼠来源的神经干细胞产生神经突的细胞比例及神经突的长度明显小于正常小鼠来源的神经干细胞．而加入galanin或受体激动剂GAL2—11后．该神经干细胞则在产生神经突的细胞比例及神经突的长度都明显上升。受体拮抗剂M35的添加可减弱galanin或GAL2-11所产生的作用。这些结果表明galanin及其受体与神经干细胞的分化及神经突的生长有着密切的联系．并可能参与了神经系统的发育。     

Kalirin Signaling: Implications for Synaptic Pathology

Spine morphogenesis and plasticity are intimately linked to cognition, and there is strong evidence that aberrant regulation of spine plasticity is associated with physiological, behavioral, and pathological conditions. The neuronal guanine nucleotide exchange factor (GEF) kalirin is emerging as a key regulator of structural and functional plasticity at dendritic spines. Here, we review recent studies that have genetically and functionally linked kalirin signaling to a number of human disorders. Kalirin signaling may thus represent a disease mechanism and provide a novel therapeutic target.     

大鼠脑内caveolin-1蛋白的表达及其在分辨学习中的作用

Caveolin-1（Cav—1）蛋白作为细胞质膜结构小窝（caveolae）的标志蛋白,在胆固醇运输、膜组装、信号转导和细胞转化过程中扮演重要的角色。为了探讨Cav-1蛋白在中枢神经系统可塑性及学习记忆中的作用,本文以Sprague—Dawley大鼠为实验对象,利用蛋白质免疫印迹杂交方法观察了Car-1蛋白在不同年龄大鼠脑内表达的特征,并研究了Y-迷宫训练前后Cav-1蛋白表达的变化。结果表明：（1）大鼠不同脑区Cav-1蛋白表达的年龄特征不同。海马内的表达属青年鼠最高,其次是老年鼠和幼年鼠;皮层内的表达属幼年鼠最高,其次是老年鼠,青年鼠最低;小脑内的表达无明显年龄差异。（2）Y-迷宫训练引起青年鼠海马和前额叶皮层内Cav-1蛋白的表达显著增加。结果提示,Cav-1蛋白与动物脑发育和学习记忆有密切关系,可能参与中枢可塑性的调节。     

A transgenic mouse class-III beta tubulin reporter using yellow fluorescent protein

A yellow fluorescence protein (YFP) reporter construct was cloned downstream of the beta-tubulin III promoter and injected to produce two founder lines of transgenic mice. YFP expression was observed in many regions of the developing peripheral and central nervous system. YFP expression was first observed in the peripheral and central nervous system as early as embryonic day 9.0. There was a dramatic increase in the number of neuronal systems expressing YFP through P0. Then as the animals reached adult age, the expression levels decreased, but many neurons still show YFP expression, notably in regions of the brain undergoing adult neurogenesis, i.e., the rostral migratory stream and subgranular layer of the dentate gyrus. This reporter-based staining was compared with anti-class-III beta-tubulin immunocytochemistry and shown to closely parallel the expression of the endogenous protein. These transgenic lines should provide unique models to study in vivo and in vitro neurodevelopment.     

The cell cycle associated protein, HTm4, is expressed in differentiating cellsof the hematopoietic and central nervous system in mice

HTm4 is a member of a newly defined family of human and murine proteins, the MS4 (membrane-spanning four) protein group, which has a distinctive four-transmembrane structure. MS4 protein functions include roles as cell surface signaling receptors and intracellular adapter proteins. We have previously demonstrated that HTm4 regulates the function of the KAP phosphatase, a key regulator of cell cycle progression. In humans, the expression of HTm4 is largely restricted to cells of the hematopoietic lineage, possibly reflecting a causal role for this molecule in differentiation/proliferation of hematopoietic lineage cells. In this study, we show that, like the human homologue, murine HTm4 is also predominantly a hematopoietic protein with distinctive expression patterns in developing murine embryos and in adult animals. In addition, we observed that murine HTm4 is highly expressed in the developing and adult murine nervous system, suggesting a previously unrecognized role in central and peripheral nervous system development.JLK and XY contributed equally to this work     

<Emphasis Type="Italic">Engrailed</Emphasis> is expressed in larval development and in the radial nervous system of <Emphasis Type="Italic">Patiriella</Emphasis> sea stars

We documented expression of the pan-metazoan neurogenic gene engrailed in larval and juvenile Patiriella sea stars to determine if this gene patterns bilateral and radial echinoderm nervous systems. Engrailed homologues, containing conserved En protein domains, were cloned from the radial nerve cord. During development, engrailed was expressed in ectodermal (nervous system) and mesodermal (coeloms) derivatives. In larvae, engrailed was expressed in cells lining the larval and future adult coeloms. Engrailed was not expressed in the larval nervous system. As adult-specific developmental programs were switched on during metamorphosis, engrailed was expressed in the central nervous system and peripheral nervous system (PNS), paralleling the pattern of neuropeptide immunolocalisation. Engrailed was first seen in the developing nerve ring and appeared to be up-regulated as the nervous system developed. Expression of engrailed in the nerve plexus of the tube feet, the lobes of the hydrocoel along the adult arm axis, is similar to the reiterated pattern of expression seen in other animals. Engrailed expression in developing nervous tissue reflects its conserved role in neurogenesis, but its broad expression in the adult nervous system of Patiriella differs from the localised expression seen in other bilaterians. The role of engrailed in patterning repeated PNS structures indicates that it may be important in patterning the fivefold organisation of the ambulacrae, a defining feature of the Echinodermata.     

Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells

Recent evidence suggests that adult neural stem/progenitor cells (ANSCs) secrete autocrine/paracrine factors and that these intrinsic factors are involved in the maintenance of adult neurogenesis. We identified a novel secretory molecule, stem cell-derived neural stem/progenitor cell supporting factor (SDNSF), from adult hippocampal neural stem/progenitor cells by using the signal sequence trap method. The expression of SDNSF in adult central nervous system was localized to hippocampus including dentate gyrus, where the neurogenesis persists throughout life. In induced neurogenesis status seen in ischemically treated hippocampus, the expression of SDNSF was up-regulated. As functional aspects, SDNSF protein provided a dose-dependent survival effect for ANSC following basic fibroblast growth factor 2 (FGF-2) withdrawal. ANSCs treated by SDNSF also retain self-renewal potential and multipotency in the absence of FGF-2. However, SDNSF did not have mitogenic activity, nor was it a cofactor that promoted the mitogenic effects of FGF-2. These data suggested an important role of SDNSF as an autocrine/paracrine factor in maintaining stem cell potential and lifelong neurogenesis in adult central nervous system.     

Identification and structural characterization of the neuronal luteinizing hormone receptor associated with sensory systems

The luteinizing hormone receptor (LHR) is a G protein-coupled receptor involved in regulation of ovarian and testicular functions. Here we show that the receptor is present also in specific areas of the peripheral and central nervous system and may thus have a broader functional role than has been anticipated. Full-length LHR mRNA and two receptor protein species of M(r) 90,000 and 73,000, representing mature and precursor forms, respectively, were expressed in adult and developing rat nervous tissue, starting at fetal day 14.5. The receptor was capable of ligand binding because it was purified by ligand affinity chromatography, and human chorionic gonadotropin and LH were able to displace (125)I-labeled human chorionic gonadotropin binding to fetal head membranes in a dose-dependent manner. Finally, two 5'-flanking sequences ( approximately 2 and 4 kb) of the rat LHR gene were shown to direct expression of the lacZ reporter to specific areas of the peripheral and central nervous system in fetal and adult transgenic mice, especially to structures associated with sensory, memory, reproductive behavior, and autonomic functions. Importantly, the transgene activity was confined to neurons and colocalized with the cytochrome P450 side chain cleavage enzyme. Taken together, these results indicate that the neuronal LHR is a functional protein, implicating a role in neuronal development and function, possibly by means of regulating synthesis of neurosteroids.     

免疫组织化学方法检测脑红蛋白在大鼠中枢神经系统的分布

目的 探讨脑红蛋白（NGB）基因在中枢神经系统中的分布。方法 用免疫组织化学ABC法研究了NGB蛋白在成年大鼠脑内的分布和定位。结果 NGB蛋白在成年大鼠脑中有非常广泛的表达。其分布区域包括大脑皮质,海马,丘脑和下丘脑的部分核团,脑桥及小脑,NGB免疫反应阳性物质定位于神经元的细胞质。结论 NGB蛋白在大鼠脑中有非常广泛的表达,提示NGB基因在中枢神经系统的功能活动中可能起重要作用。