星形胶质细胞的生物学功能及其与疾病的关系研究进展

星形胶质细胞As为中枢神经系统内多种胶质细胞中的一种.在正常中枢神经组织中,胶质细胞与神经元的比例是10:1~50:1,而星形胶质细胞在脑内数目最多,是中枢神经系统中最主要的大胶质细胞,并具有复杂多样的结构与功能.神经元-星形胶质细胞作为神经系统功能单位,它们之间的相互作用在中枢神经系统中非常重要,参与了中枢神经系统从胚胎发生到老化的各个活动,贯穿了神经元的整个发育过程.随着对中枢神经系统疾病病理机制和治疗手段的深入研究,人们认识到在神经系统发育、突触传递、神经组织修复与再生、神经免疫及多种神经疾病的病理方面都与星形胶质细胞密不可分.对星形胶质细胞的生物学功能及其与疾病的关系进行了较为系统的阐述,以期为相关疾病的临床治疗提供参考.     

小胶质细胞内的钙离子信号的研究进展

细胞内钙离子(Ca~(2+))对多种生理活动均具有一定的调节作用,它可影响神经递质释放和细胞兴奋性.细胞内钙离子浓度([Ca~(2+)]i)受到多方面调控,[Ca~(2+)]i的变化是重要的信号转导方式之一.小胶质细胞是中枢神经系统中固有的免疫细胞,它们对脑损伤、脑炎症和多种神经退行性疾病有先天性的免疫应答.除了在疾病发生发展中的作用,小胶质细胞也在很大程度上参与了神经元网络的发育和脑组织稳态的维持.受体介导的钙离子信号的传递,是包括小胶质细胞在内的所有细胞中最普遍的信号转导机制.小胶质细胞功能变化与小胶质细胞内钙离子信号的变化密切相关,对小胶质细胞内钙离子信号的研究具有重大的意义.     

神经干细胞移植的研究近况

神经干细胞能够再生和自我更新,并可以分化为神经元、星形胶质细胞和少突胶质细胞,因而神经干细胞移植可用于神经变性、脊髓损伤和神经脱髓鞘等疾病的治疗.本文主要总结了神经干细胞移植在帕金森氏病、脱髓鞘症、脊髓损伤、阿耳茨海默氏病和脑中风治疗中的应用.     

胶质细胞与药物成瘾

药物成瘾是一种慢性和复发性脑病.传统的观念认为胶质细胞在药物成瘾中仅起辅助作用.目前发现胶质细胞上存在众多的神经递质受体和转运体,且能分泌多种氨基酸、多肽、神经营养因子及炎症因子,对神经递质的代谢、神经冲动的传导以及突触的调节等起着重要的作用；且胶质细胞在药物成瘾中发生极大变化.对中枢神经系统中的星形胶质细胞、小胶质细...     

神经醇磷脂的生物学功能和细胞病理

神经醇磷脂广泛存在于所有真核生物细胞中，包括神经鞘髓磷脂、酰基鞘氨醇，脑苷类和神节甙脂类，神经醇磷脂参与重要的细胞生理活动，神经元的生长，细胞的能 性，细胞的调控等都与神经醇磷脂有关；另外，神经醇磷脂的异常还会导致一些疾病，如高歇氏病，疟疾，细胞的恶性生长等。     

神经病理性疼痛的小胶质细胞机制

小胶质细胞是中枢神经系统内重要的免疫细胞,起递呈抗原、吞噬病原体、分泌多种细胞因子和神经修复的作用。神经损伤后,小胶质细胞会被激活,可释放大量的细胞因子、炎性介质,激活补体,引起神经炎症和神经免疫反应,导致各种神经功能紊乱,引起痛觉过敏和异常痛敏。本文从小胶质细胞的激活、以及激活途径的关键分子TLR4来探讨神经病理性疼痛的发病机制。     

阿片成瘾中的神经免疫机制

综述小胶质细胞参与阿片类物质成瘾行为的细胞和分子机制,以及神经免疫抑制剂防治阿片成瘾的研究进展。阿片类物质成瘾是严重的医学和社会问题。目前针对阿片成瘾的研究主要集中在神经元,戒毒药物也主要针对阿片受体,然而其效果有限。神经元不是神经通路的唯一组分,神经小胶质细胞占中枢神经系统细胞总数的10%~15%,然而其作用和功能一度被忽视。阿片能激活Toll样受体4(TLR4),活化小胶质细胞,分泌大量炎症因子,从而调节奖赏信号通路,增加神经元兴奋性,参与成瘾行为的形成和表现。研究调节性神经免疫因子以及它们所造成神经炎症反应,将为理解阿片所造成的大脑功能改变和成瘾行为提供新的思路。     

色素上皮源性因子——一种新的神经营养和保护因子

PEDF是最近发现的一种神经营养因子，在许多组织均由表达。它具有强大的营养和保护神经作用。已有研究显示其作用机制主要涉及N-端结构域，改变细胞内钙离子，影响其它因子和胶质细胞而发挥作用等等。它对于神经疾病的治疗可能具有很大的潜力。     

犬瘟热的神经性病理机制

犬瘟热病毒(Canine distemper,CDV)可以诱发犬产生严重的免疫抑制和神经性疾病,例如脱髓鞘脑脊髓炎(demyelinating leukoencephalitis,DL),脱髓鞘是具有代表性的神经性病症。犬瘟的神经病理机制研究发现,在脱髓鞘急性损伤期,少突胶质细胞代谢障碍及小胶质细胞活化;在脱髓鞘的慢性期,免疫系统逐渐恢复,在脱髓鞘斑区发生炎症,促使损伤的恶化。研究发现:犬瘟热病毒可以存在于炎性脱髓鞘损伤区外且逃避免疫识别,这是慢性炎症性脱髓鞘损伤的主要机制,而逃避免疫识别的机制是病毒的非溶细胞性的选择性传播及限制性的感染。     

神经胶质细胞与HIV相关神经认知障碍

HIV-1相关神经认知障碍(HIV-1 associated neurocognitive disorder,HAND)是艾滋病患者中枢神经系统(central nervous system,CNS)的常见并发症,其患病率高达40%~60%,是40岁以下成人痴呆的最主要原因之一;患者从确诊到死亡的平均时间约为4~6个月,且其发病机理尚待研究.已有的研究表明,HIV-1不感染神经元,但在HAND的发病机制中,神经胶质细胞的过度活化和由此而引发的神经炎症起着重要的作用.本文就神经胶质细胞在HAND的发生发展中的作用进展进行综述.     

The myeloid cells of the central nervous system parenchyma

A microglial cell is both a glial cell of the central nervous system and a mononuclear phagocyte, which belongs to the haematopoietic system and is involved in inflammatory and immune responses. As such, microglia face a challenging task. The neurons of the central nervous system cannot divide and be replenished, and therefore need to be protected against pathogens, which is a key role of the immune system, but without collateral damage. In addition, after physical injury, neural cells need restorative support, which is provided by inflammatory responses. Excessive or chronic inflammatory responses can, however, be harmful. How microglia balance these demands, and how their behaviour can be modified to ameliorate disorders of the central nervous system, is becoming clear.     

神经炎症与神经退行性疾病

 在脑损伤、感染等应激条件的诱导下,中枢神经系统中的小胶质细胞会迅速活化并促进神经炎症的发生。神经退行性疾病中同样存在广泛的慢性神经炎症,神经炎症还可能直接参与诱导了疾病的发生。对阿尔茨海默病等多种神经退行性疾病中炎症的活化机制,以及炎症如何诱导疾病发生和加重疾病进程的前沿研究进展进行了综述。提出找到那些靶向小胶质细胞活化关键位点,并具有良好血脑屏障通透性的药物是下一步的重点研究目标。     

UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis

Microglia, brain immune cells, engage in the clearance of dead cells or dangerous debris, which is crucial to the maintenance of brain functions. When a neighbouring cell is injured, microglia move rapidly towards it or extend a process to engulf the injured cell. Because cells release or leak ATP when they are stimulated or injured, extracellular nucleotides are thought to be involved in these events. In fact, ATP triggers a dynamic change in the motility of microglia in vitro and in vivo, a previously unrecognized mechanism underlying microglial chemotaxis; in contrast, microglial phagocytosis has received only limited attention. Here we show that microglia express the metabotropic P2Y6 receptor whose activation by endogenous agonist UDP triggers microglial phagocytosis. UDP facilitated the uptake of microspheres in a P2Y6-receptor-dependent manner, which was mimicked by the leakage of endogenous UDP when hippocampal neurons were damaged by kainic acid in vivo and in vitro. In addition, systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in messenger RNA encoding P2Y6 receptors that colocalized with activated microglia were observed. Thus, the P2Y6 receptor is upregulated when neurons are damaged, and could function as a sensor for phagocytosis by sensing diffusible UDP signals, which is a previously unknown pathophysiological function of P2 receptors in microglia.     

Inflammation and therapeutic vaccination in CNS diseases

The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit.     

马钱子苷对小胶质细胞活化的抑制作用

为探讨不同浓度的马钱子苷对小胶质细胞活化的抑制作用及其相关分子机制，分离培养了小鼠原代小胶质细胞，用不同浓度的马钱子苷（50、100、200 μmol/L）预处理后，利用脂多糖（lipopolysacharide,LPS）诱导其活化。观察马钱子苷对LPS诱导的小胶质细胞活化、炎症因子释放以及NF-κB信号通路的影响。结果显示:与对照组相比，LPS组小胶质细胞胞体膨大，分泌大量炎症细胞因子，且NF-κB核转移程度增加（P<0.05），小胶质细胞呈明显的M1型活化状态；低、中、高浓度的马钱子苷干预后，小胶质细胞的细胞总面积和细胞核面积显著减少（P<0.05）；中、高浓度的马钱子苷能使TNF-α、IL-6和IL-1β的mRNA表达水平降低（P<0.05）；中浓度的马钱子苷下调TNF-α和IL-1β的蛋白质水平（P<0.05）；此外低、中、高浓度的马钱子苷可以抑制小胶质细胞内iNOS表达和NF-κB信号通路激活。上述结果表明，马钱子苷可明显抑制小胶质细胞活化，减少炎症因子释放，其作用机制可能与抑制NF-κB信号通路有关。这为马钱子苷应用于神经炎症的预防和治疗奠定了理论基础。     

An IgG autoantibody which inactivates C1-inhibitor

Antibodies are considered to play a specific pathogenic role in certain disease states such as myasthenia gravis, Graves' disease and autoimmune haemolytic anaemia. Autoantibodies which interfere with the function of enzyme cascade systems have also been described in diseases such as acquired haemophilia (anti-factor VIII antibodies) and glomerulonephritis (C3 nephritic factor). The identification of these autoantibodies is crucial to an understanding of the aetiology of such diseases and is also of importance in revealing the inter-relationships of the immune system with other biological pathways. This is the first report of an immunoglobulin G (IgG) autoantibody reactive with C1-inhibitor (C1-Inh), a pivotal inhibitor of the inflammatory response which is known to inactivate proteins of the complement, kinin, fibrinolytic and 'contact phase' systems. This autoantibody was isolated from a patient with a novel variant of acquired angioedema and C1-Inh dysfunction. This finding highlights the involvement of the immune system in the pathogenesis of disorders characterized by the presence of dysfunctional inflammatory response proteins.     

脑网络组学构建分析及应用研究

大脑是自然界最为复杂的系统之一。脑网络作为复杂网络理论在神经科学中的重要应用,极大程度上表现了不同尺度的脑结构或功能连接模型,提供了解释人脑这一复杂系统在结构组织及信息加工模式等问题的重要工具。同时,脑网络在脑疾病的临床应用研究中,也已证明很多脑疾病,在网络层面中均体现了不同程度的拓扑结构差异。这些成果为在系统水平上揭示脑疾病的病理机制提供了新的思路。笔者将以脑网络研究为重点,介绍脑网络的构建方法,包括不同影像类型下节点及边的定义方法;关联矩阵的阈值选择及稀疏度的划分方法;网络度量指标的计算,包括度、小世界属性、模块化等;脑网络的比较方法及其在抑郁症的临床应用及未来可能的研究方向。     

Chiral inorganic nanostructures for theranostics

Inorganic chiral nanomaterials have attracted wide attention because of their superior physical properties and chiroptical activities. Great progress in chiral nanostructure preparation has been made, such as noble metals and semiconductors. In this review, we introduce several chiral nanomaterials with feasible biocompatibility and low cytotoxicity that are promising candidates for biological applications, and we focus on their preparation in terms of their circular dichroism (CD) effects and circular luminescence properties. Additionally, we summarize the working function of chiral nanostructures toward some common diseases with high prevalence, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), diabetes and even cancers. The introduction of inorganic chirality will provide a novel way to diagnose and treat these diseases.     

神经干细胞及其临床应用潜能

近年来神经干细胞已在成年哺乳动物中的中枢神经系统中分离成功。神经干细胞的最基本特征是具有分化为神经元、星状胶质细胞和少突胶质细胞的潜能，具有自我更新能力，并足以维持整个大脑所需。神经干细胞在修复受伤神经组织及治疗神经系统退行性疾病，如帕金森病、阿尔茨海默病、和亨庭顿病等方面有很好的应用前景。但在达到临床实际应用之前仍有一系列问题需要解决，最首要的是搞清神经干细胞的分化机制。