疯牛病诊断技术现状及前景

牛海绵样脑病(BSE)是动物传染性海绵样脑病(TSE)中的一种,潜伏期2～6年,临床上常表现出神经紧张、不安、恐惧,具有攻击性,BSE病牛的病理组织学变化多局限于中枢神经系统,用SAF的抗体对病牛脑组织切片进行免疫组织化学染色,可以检出变性的PrP 神经元的特征性病理变化常出现在延髓、小脑腹侧角处延髓、脑桥中 诊断方法有PrP的生物学测定法、组织病理学检查、PrPSc的免疫学检测(细胞免疫化学染色、免疫印迹、组织印迹、ELISA)、SAF检查和PrP基因分析等,其中的PrPSc检测对TSE的诊断具有特异性     

神经异常作为一种遗传表型在HTV-1大鼠的鉴别

第一个研制成功了HIV 1转基因鼠模型。通过大量病理学研究和继发感染发生已经证实 :HIV感染对中枢和外周神经系统产生显著的影响。最初观察这个模型的神经病理学结果与HIV 1病人中枢神经系统神经病理学和神经肌肉病变相一致。对这些鼠模型的最初观察发现 ,动物步态紊乱 ,表现为共济失调。动物表现出不安并容易兴奋 ,明显弓背 ,进行性肌肉衰弱 ,最后后肢瘫痪。显微镜检查可见明显的后肢肌肉萎缩 ,并出现中度到重度炎症变化。这对解释和探讨HIV 1神经病理学的假说是一个非常好的动物模型神经异常作为一种遗传表型在HTV-1大鼠的鉴别@邢进…     

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.     

读者之声

正神经胶质细胞真的能生成牙齿吗牙齿是人类最坚固的器官,也是咀嚼、摄取食物所必需的器官。形成牙齿的细胞被称为成牙细胞,传统观点认为,成牙细胞源自于牙髓内的间充质干细胞。而神经胶质细胞是广泛分布于中枢神经系统以及外周神经系统内的,起着支持和滋养神经元作用的一大群细胞。牙齿和神经胶质似乎是风马牛不相     

外周神经的溃变与再生

本文阐述了外周神经溃变的几种类型,诸如顺行性变性;逆行性变性;跨神经元变性及其它变性.其中包括外周神经系统的变性,也涉及到中枢神经系统.当轴突受到破坏后,几种变性都可能发生.轴突的再生过程非常重要,但它必须是在神经元胞体完好无损的情况下才能进行.此过程与几种因素相关.     

BTEX对动物发育的影响

BTEX是苯、甲苯、乙苯和三种二甲基苯异构体的合称.BTEX不仅对环境造成污染,而且对中枢神经系统发育和功能有一定的毒副作用.本文主要从BTEX的研究背景以及其对动物神经发育的影响进行阐述;围绕模式动物小鼠、斑马鱼以及非洲爪蟾展开介绍,综述BTEX处理对这些模式动物的神经发育以及形态和行为的作用,探讨BTEX神经毒性作用的内在机制,为相关疾病的预防和机制研究提供参考.     

《中国学术期刊文摘》(中文版)综述文摘选登

朊病毒致病机理的研究进展苏晓鸥(中国农业大学国家动物海绵状脑病实验室,北京100094)就细胞型朊蛋白PrPc的分子生物学特性、朊蛋白的生理功能、致病性朊蛋白PrPsc对免疫系统的影响、朊病毒的外周致病     

马脑髓鞘碱性蛋白的纯化和鉴定

髓鞘碱性蛋白(Myelin Basic Protein,MBP)存在于哺乳动物中枢神经系统组织,是神经髓鞘的主要蛋白质成分之一,约占总髓鞘的30％。人或动物经连续性病毒感染,受外源抗原物质MBP的触发,产生抗MBP抗体,引起自身免疫性脱髓鞘疾病,同时向体液释放MBP及其降解肽。测定患者体液中MBP含量,可作为诊断和愈后监测该疾病的临床依据。MBP的提纯、鉴定对阐明脱髓鞘疾病的病理和临床研究具有重要意义。近年来,Bashir等人对人、灵长类及偶蹄目哺乳动物MBP作了较详细的研究,而对奇蹄目动物MBP的研究,报导甚少。本文以中国蒙古马脑为材料,进行MBP的提纯和鉴定。     

人类朊蛋白稳定性的流体分子动力学研究（英文）

朊蛋白病,被称为传染性海绵状脑病(TSE),或者致死性神经退行传染病,在人和动物中发病,与α-螺旋构型部分向β-折叠构型转变有关.本文使用分子动力学模拟和流体分子动力学模拟相结合的方法对野生型人类朊蛋白和R200K突变型人类朊蛋白的结构稳定性进行了研究.研究发现,α-螺旋柱交叉形成的防护墙是维持朊蛋白结构稳定的关键因素,而β-折叠活性较高.流体动力干扰在一定程度上可以不改变折叠路径并能够有效加速蛋白质的解折叠过程.     

马脑髓鞘碱性蛋白的纯化和鉴定

髓鞘碱性蛋白(Myelin BasicProtein,MBP)存在于哺乳动物中枢神经系统组织,是神经髓鞘的主要蛋白质成分之一,约占总髓鞘的30%.人或动物经连续性病毒感染,受外源抗原物质MBP的触发,产生抗MBP抗体,引起自身免疫性脱髓鞘疾病,同时向体液释放MBP及其降解肽.测定患者体液中MBP含量,可作为诊断和愈后监测该疾病的临床依据.MBP的提纯、鉴定对阐明脱髓鞘疾病的病理和临床研究具有重要意义. 近年来,Bashir等人对人、灵长类及偶蹄目哺乳动物MBP作了较详细的研究,而对奇蹄目动物     

Transmissible and genetic prion diseases share a common pathway of neurodegeneration

Prion diseases can be infectious, sporadic and genetic. The infectious forms of these diseases, including bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, are usually characterized by the accumulation in the brain of the transmissible pathogen, an abnormally folded isoform of the prion protein (PrP) termed PrPSc. However, certain inherited PrP mutations appear to cause neurodegeneration in the absence of PrPSc, working instead by favoured synthesis of CtmPrP, a transmembrane form of PrP. The relationship between the neurodegeneration seen in transmissible prion diseases involving PrPSc and that associated with ctmPrP has remained unclear. Here we find that the effectiveness of accumulated PrPSc in causing neurodegenerative disease depends upon the predilection of host-encoded PrP to be made in the ctmPrP form. Furthermore, the time course of PrPSc accumulation in transmissible prion disease is followed closely by increased generation of CtmPrP. Thus, the accumulation of PrPSc appears to modulate in trans the events involved in generating or metabolising CtmPrP. Together, these data suggest that the events of CtmPrP-mediated neurodegeneration may represent a common step in the pathogenesis of genetic and infectious prion diseases.     

Antibodies inhibit prion propagation and clear cell cultures of prion infectivity

Prions are the transmissible pathogenic agents responsible for diseases such as scrapie and bovine spongiform encephalopathy. In the favoured model of prion replication, direct interaction between the pathogenic prion protein (PrPSc) template and endogenous cellular prion protein (PrPC) is proposed to drive the formation of nascent infectious prions. Reagents specifically binding either prion-protein conformer may interrupt prion production by inhibiting this interaction. We examined the ability of several recombinant antibody antigen-binding fragments (Fabs) to inhibit prion propagation in cultured mouse neuroblastoma cells (ScN2a) infected with PrPSc. Here we show that antibodies binding cell-surface PrPC inhibit PrPSc formation in a dose-dependent manner. In cells treated with the most potent antibody, Fab D18, prion replication is abolished and pre-existing PrPSc is rapidly cleared, suggesting that this antibody may cure established infection. The potent activity of Fab D18 is associated with its ability to better recognize the total population of PrPC molecules on the cell surface, and with the location of its epitope on PrPC. Our observations support the use of antibodies in the prevention and treatment of prion diseases and identify a region of PrPC for drug targeting.     

Monoclonal antibodies inhibit prion replication and delay the development of prion disease

Prion diseases such as Creutzfeldt-Jakob disease (CJD) are fatal, neuro-degenerative disorders with no known therapy. A proportion of the UK population has been exposed to a bovine spongiform encephalopathy-like prion strain and are at risk of developing variant CJD. A hallmark of prion disease is the transformation of normal cellular prion protein (PrP(C)) into an infectious disease-associated isoform, PrP(Sc). Recent in vitro studies indicate that anti-PrP monoclonal antibodies with little or no affinity for PrP(Sc) can prevent the incorporation of PrP(C) into propagating prions. We therefore investigated in a murine scrapie model whether anti-PrP monoclonal antibodies show similar inhibitory effects on prion replication in vivo. We found that peripheral PrP(Sc) levels and prion infectivity were markedly reduced, even when the antibodies were first administered at the point of near maximal accumulation of PrP(Sc) in the spleen. Furthermore, animals in which the treatment was continued remained healthy for over 300 days after equivalent untreated animals had succumbed to the disease. These findings indicate that immunotherapeutic strategies for human prion diseases are worth pursuing.     

Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice

The autoimmune disease of the central nervous system (CNS), experimental allergic encephalomyelitis (EAE), is induced by challenge of genetically susceptible animals with spinal cord homogenates or myelin basic protein (MBP). Chronic and relapsing forms of the disease have some similarities to human demyelinating disorders, namely, multiple sclerosis, and are of particular interest. EAE can be transferred passively with sensitized lymphoid cells into syngeneic animals but transferred EAE has been believed to have limited relevance to human disease because it is usually monophasic and manifested by minimal demyelination. We report here that a single transfer of MBP-sensitized lymph node cells or T cell, in the absence of a peripheral antigen depot, leads to both acute EAE with significant primary demyelination, and chronic relapsing disease with lesions typical of demyelination over a long period. These findings have major implications for the immunological mechanisms involved in experimental and human demyelinating diseases.     

Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion

Peripheral infection is the natural route of transmission in most prion diseases. Peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion and progressive neurological disease. Both immune cells and nerves are involved in pathogenesis, but the mechanisms of prion transfer from the immune to the nervous system are unknown. Here we show that ablation of the chemokine receptor CXCR5 juxtaposes follicular dendritic cells (FDCs) to major splenic nerves, and accelerates the transfer of intraperitoneally administered prions into the spinal cord. Neuroinvasion velocity correlated exclusively with the relative locations of FDCs and nerves: transfer of CXCR5-/- bone marrow to wild-type mice induced perineural FDCs and enhanced neuroinvasion, whereas reciprocal transfer to CXCR5-/- mice abolished them and restored normal efficiency of neuroinvasion. Suppression of lymphotoxin signalling depleted FDCs, abolished splenic infectivity, and suppressed acceleration of pathogenesis in CXCR5-/- mice. This suggests that prion neuroimmune transition occurs between FDCs and sympathetic nerves, and relative positioning of FDCs and nerves controls the efficiency of peripheral prion infection.     

Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1

Myelin-associated glycoprotein (MAG) is a quantitatively minor component in both peripheral and central myelin sheaths that is thought to have a role in cell-cell interactions within the nervous system. We show here that a mouse monoclonal antibody, HNK-1, which is directed against human natural killer cells also recognizes an antigenic determinant of human central and peripheral nervous system white matter by immunoperoxidase staining of tissue sections. Immunoblot analysis of myelin proteins and purified extracted MAG indicates that the antigen recognized is MAG.     

“疯牛病”与“疯人病”——蛋白粒与蛋白粒疾病

蛋白粒是一个不含核苷酸的蛋白性粒子,能够传染动物和人．引起大脑损伤及死亡．蛋白粒疾病包括羊瘙痒病、牛海绵体脑炎、人的克氏-约氏病、杰氏-斯氏-斯氏病以及致命性家族失眠症．本文从蛋白粒与人类和动物疾病的关系,回顾了蛋白粒疾病发生及传染的过程．具有不同氨基酸组成的蛋白粒,存在着可溶性的ＰｒＰC型及不溶性ＰｒＰＳＣ型．只有ＰｒＰＳＣ是传染性的．通过对蛋白粒结构与功能的剖析,讨论了蛋白粒的基因、蛋白粒的产生以及可能的致病机理（Ｘ蛋白被发现与细胞内蛋白粒增生有关）．最后,对蛋白质、ＤＮＡ和ＲＮＡ之间的遗传信息流提出了一个新的假说．     

Advances in research on Shadoo,shadow of prion protein

Prion plays a central role in the pathogenesis of transmissible spongiform encephalopathies, also known as prion diseases. However, the biology of the protein and the pathophysiology of these diseases remain largely unknown. It has been speculated that additional factor or factors may be involved in the pathogenesis of prion diseases. Recently, a PrP-like protein, recognized as shadow of prion protein （Shadoo, Sho）, is thought to be an interesting candidate factor because both the prion protein and Sho have been shown to have overlapping expression patterns and shared functions. Therefore, extensive study of Sho may advance our understanding of the enigmatical biology of prion and prion diseases. In this review, recent studies on Sho asso- ciated with prion diseases and functions are summarized. These studies have demonstrated the functional importance of Sho, and they further need to investigate its biological roles in prion diseases.     

Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease.

The human prion diseases, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str?ussler syndrome (GSS), are neurodegenerative diseases that are unique in being both infectious and genetic. Transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented. Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal dominant diseases. More than 80% of CJD cases occur sporadically, however, and are not known to be associated with mutations. Here we report that 21 of 22 sporadic CJD cases and a further 19 of 23 suspected sporadic CJD cases are homozygous at the polymorphic amino-acid residue 129; 51% of the normal population are heterozygous at this site. We argue that homozygosity predisposes towards sporadic CJD and that this directly supports the hypothesis that interaction between prion protein molecules underlies the disease process.     

A shared antigenic determinant between natural killer cells and nervous tissue

Considerable evidence for shared antigenic determinants between nervous elements and lymphocytes has accumulated. It has also been suggested that this cross-recognition may be involved in the pathogenesis of human neurological diseases such as myasthenia gravis and multiple sclerosis. We report here evidence that a marker for natural killer (NK) cells, anti-Leu-7 (HNK-1), specifically binds to components of human and rodent central nervous tissue as well as peripheral nervous tissue, especially to myelin sheaths. In contrast, another NK-cell marker (VEP13) did not react with nervous tissue. Since NK-cell function is impaired in a population of multiple sclerosis patients, the observed cross-reactivity indicates that autosensitization against myelin may simultaneously cause a defect of NK-cell function. Furthermore, the shared antigenic determinant may help to identify a hitherto undefined nervous tissue antigen and simultaneously increase the knowledge about the nature of NK-cell antigens.