内源性神经节苷脂GM1与神经系统发育的关系

神经节苷脂GM1是膜表面一类重要的鞘糖脂 ,与神经系统发育密切相关。神经节苷脂GM1对神经细胞胞内钙离子浓度的调节具有重要作用。核膜神经节苷脂GM 1与神经细胞轴突生长密切相关     

神经节苷脂治疗婴幼儿大脑性瘫痪临床研究

目的：探讨神经节苷脂治疗婴幼儿大脑性瘫痪（脑瘫）的临床疗效。方法：将84例脑瘫患儿随机分为治疗组和对照组,各42例。两组性别、年龄、临床分型、伴随疾病、头颅CT及发病因素等对比差异均无显著意义（P〉0．05）。两组均采用支持、对症、脱水和降颅压等常规治疗,并予以物理疗法、针灸、按摩、高压氧等综合治疗,治疗组患儿同时加用神经节苷脂2ml（20mg）,加入5％葡萄糖注射液250m1中静脉滴注,每日1次,10d为1个疗程。停药20d后进入下一个疗程,连续治疗6个疗程。结果：与对照组相比,洽疗组治疗后发育商评分明显上升,头颅CT阳性率显著降低。治疗组总有效率为95％（40／42）与对照组的79％（33／42）相比差异有显著意义（P〈0．05）。结论：神经节苷脂治疗婴幼儿脑瘫的临床疗效确切。     

单唾液酸四己糖神经节苷脂联合复方丹参对极低出生体重儿神经系统预后的影响

目的单唾液酸四己糖神经节苷脂（GMI）与复方丹参对极低出生体重儿神经系统预后的影响。方法108例极低出生体重儿分为两组：在治疗原发病和早产儿各项并发症的基础上,治疗组在生后3天给予GM1（20mg／d）和复方丹参注射液（2ml／d）,对照组给予复方丹参注射液（2ml／d）,均连用14天为一个疗程。纠正胎龄37周后两组NBNA评分进行比较。结果纠正胎龄足月后治疗组NBNA评分明显高于不用GM1的对照组（P〈0．01）。结论GM1联用复方丹参在改善极低出生体重儿神经系统预后方面有较好的疗效。     

单唾液酸神经节苷脂（GM1）对经MPTP破坏的小鼠黑质纹状体多巴胺…

将１－甲基－４苯基－１．２．３．６四氢吡啶经腹腔注入小鼠，连续注射６天，一组动物注射后次日处死。另一组动物存活二周后处死；第三组动物在给予１－甲基－４苯基－１．２．３．６四氢吡啶的同时，经腹膜腔注射神经节苷脂持续三周；第四组为对照组。各组动物脑用酶氨酸羟化酶抗体进行免疫组化观察。     

神经节苷脂GD2和GD3在乳腺癌中作用的研究进展

神经节苷脂是含唾液酸的酸性鞘糖脂,由亲水的寡糖链和亲脂的神经酰胺两部分组成,在信号转导和细胞黏附中发挥重要作用。GD2和GD3是含有2个唾液酸而糖基数目不同的神经节苷脂,与许多肿瘤的发生、发展密切相关,如乳腺癌、胶质瘤、黑色素瘤等,且通过多种途径促进肿瘤细胞的增殖、转移。同时,随着临床研究的进展,已被证实在维持乳腺癌干细胞特性方面发挥重要作用。该文就GD2和GD3的生物学特性、在乳腺癌和乳腺癌干细胞中的作用及在临床中的作用予以综述。     

神经节苷脂GM_1对神经生长因子作用的调节

<正> 脑是一个动力学器官。中枢神经系统内的神经元能够对它们微环境内的化学信号起反应,此过程被广义地称为神经可塑性。在各种分子的调节之中神经可塑性的表达受到一些神经营养因子的调节。这些神经营养因子都是蛋白质,它们对不同种类神经元的存活、维持和修复能力发生影响,神经生长因子(NGF)就是一个典型的例子。消除神经元的靶区或阻断突触连接则使神经元丧失充分的营养支持,导致萎缩和死亡。 NGF的作用并不局限于神经元发育过程的某些固定时期,成年动物的中枢和周围神经系统的神经元均能对NGF起反应。在实验性损毁、中断海马产生的NGF向隔区的胆碱能神     

神经节苷脂肿瘤疫苗研究进展

神经节苷脂是一类细胞膜上的糖鞘脂类化合物 ,其伸展于胞膜表面的糖基具有免疫原性抗原决定簇 ,能够诱发IgM抗体反应。由于其在多种神经外胚层起源的肿瘤组织中过度表达 ,因此可作为肿瘤疫苗的靶分子。各种经过加工、处理的神经节苷脂肿瘤疫苗的免疫原性明显增强 ,诱导产生IgM及IgG。经多种动物模型及临床实验证明 ,其抗体产生的水平和持续时间与肿瘤患者的预后明显相关 ,因此在肿瘤生物治疗上是一很有前景的研究目标。     

神经节苷脂对损伤胎鼠背根神经节的保护作用

目的观察神经节苷脂(GM1)对受损伤胎鼠背根神经节(DRG)神经元形态改变的影响,探讨其可能的保护作用。方法选择胎龄为15d的SD大鼠为研究对象,获取DRG神经元并进行体外分散培养,培养48h后,随机分为对照组、谷氨酸损伤组和谷氨酸损伤+GM1保护组,继续培养12h。终止培养后,观察各组神经元的形态结构改变,用MTT法鉴定细胞的存活率。结果对照组DRG神经元细胞贴壁呈单层散在分布,少部分出现细胞聚集现象,突起较长且互相交织形成网状。谷氨酸损伤组DRG神经元细胞聚集现象明显,神经元突起变短、断裂甚至消失。谷氨酸损伤+GM1保护组DRG神经元细胞部分呈簇状聚集,部分呈单个散在分布,突起仍然相互交织。MTT结果显示谷氨酸损伤+GM1保护组细胞存活率高于谷氨酸损伤组。结论神经节苷脂可以影响损伤胎鼠DRG神经元的形态改变,对胎鼠背根神经节神经元具有一定的保护作用。     

093 神经节苷脂肿瘤疫苗研究进展

神经节苷脂是一类细胞膜上的糖鞘脂类化合物，其伸展于胞膜表面的糖基具有免疫原性抗原决定簇，能够诱发IgM抗体反应。由于其在多种神经外胚层起源的肿瘤组织中过度表达，因此可作为肿瘤疫苗的靶分子。各种经过加工、处理的神经节苷脂肿瘤疫苗的免疫原性明显增强，诱导产生IgM及IgG。经多种动物模型及临床实验证明，其抗体产生的水平和持续时间与肿瘤患者的顸后明显相关，因此在肿瘤生物治疗上是一很有前景的研究目标。     

Cranial neural crest cells on the move: their roles in craniofacial development

The craniofacial region is assembled through the active migration of cells and the rearrangement and sculpting of facial prominences and pharyngeal arches, which consequently make it particularly susceptible to a large number of birth defects. Genetic, molecular, and cellular processes must be temporally and spatially regulated to culminate in the three-dimension structures of the face. The starting constituent for the majority of skeletal and connective tissues in the face is a pluripotent population of cells, the cranial neural crest cells (NCCs). In this review we discuss the newest scientific findings in the development of the craniofacial complex as related to NCCs. Furthermore, we present recent findings on NCC diseases called neurocristopathies and, in doing so, provide clinicians with new tools for understanding a growing number of craniofacial genetic disorders.     

The roles of chemokines in the development of systemic sclerosis

Systemic sclerosis (SSc, scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition and vascular injury in the skin and internal organs. Although the pathogenesis remains unclear, Raynaud's phenomenon, a kind of ischemia-reperfusion, usually precedes the development of skin sclerosis. Therefore, it is possible that endothelial cell injury caused by recurring ischemia-reperfusion induces inflammatory cell infiltration and subsequent cytokine production, leading to the development of tissue fibrosis. During this process, chemokines likely have important roles via mediating chemotaxis and activation of leukocytes, result in the interaction between leukocytes and fibroblasts. While chemokine abnormalities of SSc have been reported in amounts of literatures, monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, CCR2, likely have the most critical role for the development of SSc. Here recent data will be reviewed on the potential role of chemokines and their receptors in SSc.     

The potential roles for embryotrophic ligands in preimplantation embryo development

Identification of the role(s) extracellular ligands play in regulating the development of the mammalian preimplantation embryo is a controversial area. Unequivocal evidence for their role is complicated by the apparent overlapping actions of multiple ligands. The discovery that the embryo also releases its own repertoire of ligands and expresses their corresponding receptors has further constrained analysis of their roles. Conventional ligand ablation strategies have limited utility when the cell responding to multiple ligands also produces them. The application of methods for identifying signal transduction events that occur in the early embryo in response to ligands has allowed direct assessment of the actions of these putative trophic ligands. A range of ligands induce phosphatidylinositol-3-kinase mediated survival signalling, and this is required for normal embryo development. Survival signalling maintains apoptotic pathways in a latent state within normal somatic cells, and they may fulfill the same role in the early embryo. Survival signals can also mitigate the adverse response of embryos to genotoxic and non-genotoxic stressors. Currently, there is no unequivocal evidence for a direct role of these ligands in the induction of mitosis in the early embryo. Embryotrophic ligands, acting via their specific receptors, to activate a network of effectors to create pro-survival, anti-apoptotic settings within the preimplantation embryo and these are required for normal embryo survival.     

The various and shared roles of lncRNAs during development

lncRNAs, genes transcribed but not translated, longer than 200 nucleotides, are classified as a separate class of nonprotein coding genes. Since their discovery, largely from RNAseq data, a number of pioneer studies have begun to unravel its myriad functions, centered on gene expression regulation, suggesting developmental and evolutionary conservation. Since they do not code for proteins and have no open reading frames, their functional constraints likely differ from that of protein coding genes, or of genes where the majority of the nucleotide sequence is required for function, like tRNAs. This has complicated assessment of both developmental and evolutionary conservation, and the identification of homologs in different species. Here we argue that other characteristics: general synteny and particular chromosomal placement regardless of sequence, sequence micro-motifs, and secondary structure allow for “homologs” to be identified and compared, confirming developmental and evolutionary conservation of lncRNAs. We conclude exemplifying a case in point: that of the evolutionarily conserved lncRNA acal, characterized and required for embryogenesis in Drosophila.     

The development of the neural crest in the human

The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following. (1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10. (2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5. (3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube. (4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds. (5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer. (6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion. (7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9-14. (8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical. (9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest. (10) The hypoglossal crest provides cells that accompany those of myotomes 1-4 and form the hypoglossal cell cord at stages 13 and 14. (11) The occipital crest, which is related to somites 1-4 in the human, differs from the spinal mainly in that it does not develop ganglia. (12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter. (13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull.     

The many roles of dystroglycan in nervous system development and function

The glycoprotein dystroglycan was first identified in muscle, where it functions as part of the dystrophin glycoprotein complex to connect the extracellular matrix to the actin cytoskeleton. Mutations in genes involved in the glycosylation of dystroglycan cause a form of congenital muscular dystrophy termed dystroglycanopathy. In addition to its well-defined role in regulating muscle integrity, dystroglycan is essential for proper central and peripheral nervous system development. Patients with dystroglycanopathy can present with a wide range of neurological perturbations, but unraveling the complex role of Dag1 in the nervous system has proven to be a challenge. Over the past two decades, animal models of dystroglycanopathy have been an invaluable resource that has allowed researchers to elucidate dystroglycan's many roles in neural circuit development. In this review, we summarize the pathways involved in dystroglycan's glycosylation and its known interacting proteins, and discuss how it regulates neuronal migration, axon guidance, synapse formation, and its role in non-neuronal cells.     

Emerging roles of MT-MMPs in embryonic development

Membrane-type matrix metalloproteinases (MT-MMPs) are cell membrane-tethered proteinases that belong to the family of the MMPs. Apart from their roles in degradation of the extracellular milieu, MT-MMPs are able to activate through proteolytic processing at the cell surface distinct molecules such as receptors, growth factors, cytokines, adhesion molecules, and other pericellular proteins. Although most of the information regarding these enzymes comes from cancer studies, our current knowledge about their contribution in distinct developmental processes occurring in the embryo is limited. In this review, we want to summarize the involvement of MT-MMPs in distinct processes during embryonic morphogenesis, including cell migration and proliferation, epithelial-mesenchymal transition, cell polarity and branching, axon growth and navigation, synapse formation, and angiogenesis. We also considered information about MT-MMP functions from studies assessed in pathological conditions and compared these data with those relevant for embryonic development.