NG2细胞的研究进展

NG2细胞,是在发育和成年中枢神经系统的灰质和白质束中发现的,因表达NG2蛋白多糖而得名.NG2细胞先前被假定代表少突胶质细胞前体细胞,后来使用转基因小鼠的研究表明,NG2细胞在体内不仅能够产生少突胶质细胞,还能产生原浆性星形胶质细胞,以及某些情况下的神经元[1].NG2细胞是中枢神经系统中不同于神经元、成熟少突胶质细胞、星形胶质细胞和小胶质细胞的一类细胞亚群.此外,在发育和成年中枢神经系统的多个区域,发现NG2细胞和神经元之间存在独特的突触联系,暗示NG2细胞除了可能作为分化成多种细胞的可塑性前体细胞群,还可能会和神经元联系从而形成一个独特的神经胶质网络[2].进行综述对NG2细胞的近年研究,以及其功能特性和在神经网络中所扮演的角色.     

NG2胶质细胞在中枢神经系统病变中作用的研究进展

NG2胶质细胞是中枢神经系统中除星形胶质细胞、小胶质细胞和少突胶质细胞外的第四类胶质细胞,均匀地分布在整个脑区。当中枢神经系统发生损伤时,NG2胶质细胞能通过改变其细胞形态、增殖和分化对多种损伤类型作出反应。弄清NG2胶质细胞对不同损伤的反应机制,有助于更好地发挥其在损伤修复和髓鞘再生中的作用。本文着重讨论了NG2胶质细胞在几种损伤类型中的反应。     

NG2与中枢神经系统疾病研究新进展

<正>NG2是一种硫酸软骨素蛋白多糖(chondroitin sulphate peoteoglycan,CSPG),在发育及成熟哺乳动物中枢神经系统中广泛表达。表达NG2的细胞根据其密度、分布、独特的细胞标记和生理性能归为一类独特的神经胶质细胞。NG2细胞具有神经干细胞的部分特性和分化产生不同细胞系的潜     

小胶质细胞与NG2胶质细胞相互作用研究进展

小胶质细胞是大脑的固有免疫细胞,在中枢神经系统的发育和稳态中起着重要的作用。NG2胶质细胞被认为是少突胶质细胞的前体细胞。近年来的研究表明,NG2胶质细胞与其他神经胶质细胞也存在广泛的相互作用,参与大脑神经免疫反应。加强对小胶质细胞和NG2胶质细胞之间相互作用的认识将有助于发现大脑中免疫调节的新途径,有利于神经炎症和神经退行性疾病的治疗,本文将对这两种细胞之间的相互作用进行综述。     

WNT/β-catenin信号调节神经干细胞向少突胶质-GABA能神经元分化的体外研究

目的:在体外研究Wnt/β-catenin信号对于少突胶质-GABA能神经元前体细胞分化的影响。方法:培养胎鼠中脑神经干细胞,在Wnt3a刺激或过表达β-catenin的条件下进行诱导分化,采用免疫细胞化学染色和Western Blot检测Wnt/β-catenin信号激活时,少突胶质-GABA能神经元共同前体细胞标记蛋白DLX2,少突胶质细胞标记蛋白NG2,GABA能神经元标记蛋白GAD67的表达。结果:Western Blot显示Wnt-3a处理上调β-catenin和Wnt/β-catenin信号下游靶基因cyclin D1和Axin2的表达;Wnt3a处理和过表达β-catenin的神经干细胞可显著上调Dlx2,NG2和GAD67阳性细胞的百分率(P0.05)。Wnt3a刺激和β-catenin过表达均抑制神经干细胞向星型胶质细胞方向的分化。结论:Wnt/β-catenin信号可在体外促进神经干细胞向GABA能神经元和少突胶质细胞方向分化。     

星形胶质细胞与运动神经元的相关关系

星形胶质细胞作为中枢神经系统中最丰富的神经胶质细胞,是中枢神经系统最主要的支持细胞,为神经元提供营养支持和保护作用。在肌萎缩脊髓侧索硬化症(ALS)发病过程中,退行性病变的神经元以及过度激活的胶质细胞将导致神经元所处微环境恶化,使神经元的损伤进行性加重。因此,研究星形胶质细胞与运动神经元的关系对探讨ALS的发病机制及其干预治疗具有非常重要的意义。     

星形胶质细胞转分化为神经元在神经再生中的研究进展

<正>星形胶质细胞是广泛存在于中枢神经系统内的一类胶质细胞,在建立和维持正常脑功能以及脑损伤后修复中具有重要作用。近几年发现,特定区域脑损伤后星形胶质细胞发生活化,甚至转分化为神经元谱系,表现出类似于神经前体细胞的特性,这一重要的潜能使得星形胶质细胞成为神经再生领域研究的焦点。本文就星形胶质细胞的基本特性、其转分化为神经元的模型以及介导转分化发生的细胞与分子学     

NG2~+胶质细胞在Th1-EAE和Th17-EAE中的不同作用

NG2~+胶质细胞在EAE中的作用还不清楚。课题组应用PDGFRα-CreER特异地诱导白喉毒素在NG2~+胶质细胞中表达,成功地在小鼠中枢神经系统中部分剔除NG2~+胶质细胞。研究发现部分剔除NG2~+胶质细胞的小鼠CNS中在诱导Active-EAE和Th1-EAE的发病过程中,表现为临床症状减轻、髓鞘蛋白脱落减少以及炎症细胞浸润减少,说明NG2~+胶质细胞能够增强胶质细胞的作用以加重Active-EAE和Th1-EAE的发病程度。与此相反,在Th17-EAE小鼠中,NG2~+胶质细胞能够抑制EAE的发生。这些结果提示NG2~+胶质细胞在不同诱导方式EAE发生中的作用是不同的,因此在治疗方法上也应该区别对待。这一结果将帮助多发性硬化患者的治疗提供新的靶点。     

Notch-Delta信号系统与寡突胶质细胞的发育

寡突胶质细胞来源于中枢神经系统中分化的神经干细胞,是继神经元和星形胶质细胞后出现较晚的一类细胞。它不仅参与轴突髓鞘的形成,影响神经冲动的传导,而且还维持神经元轴突的正常结构。近年来研究发现,寡突胶质细胞参与多种中枢神经系统疾病的发生和发展。因此,明确其来源和分化机制是十分必要的。寡突胶质细胞的发育成熟受多种神经营养因子、激素及信号系统的调控,其中越来越多的研究结果表明,Notch—Delta信号系统在调节寡突胶质细胞的发育上起到关键作用,本文就此研究进展做一综述。     

中枢神经系统的胶质神经元肿瘤

中枢神经系统的胶质神经冗肿瘤是含有肿瘤性神经元和胶质两种成分的神经上皮肿瘤,但不包括可以向神经细胞和胶质双向分化的胚胎性肿瘤。胶质神经元肿瘤较少见,其中相对常见的是节细胞胶质瘤,而胚胎发育不良性神经上皮肿瘤、促纤维增生性婴儿节细胞胶质瘤以及近年来陆续报道的一些具有形态特点的新的胶质神经元肿瘤,如乳头状胶质神经元肿瘤和伴有神经毡样岛或菊形团的胶质神经元肿瘤,都是少见的类型。     

Morphological and physiological interactions of NG2-glia with astrocytes and neurons

Models of central nervous system (CNS) function have historically been based on neurons and their synaptic contacts - the neuronal doctrine. This doctrine envisages glia as passive supportive cells. However, electrophysiological and imaging studies in brain slices show us that astrocytes, the most numerous cells in the brain, express a wide range of neurotransmitter receptors that are activated in response to synaptic activity. Furthermore, astrocytes communicate via calcium signals that are propagated over long distances by the release of 'gliotransmitters', the most abundant being adenosine triphosphate (ATP). This has led to the concept of the neuron-astroglial functional unit as the substrate of integration in the CNS. Recently, a novel glial cell type has been characterized by expression of the proteoglycan NG2. These NG2-glia receive presynaptic input from neurons and responds to neurotransmitters released at synapses. Now, studies on transgenic mice in which fluorescent proteins are specifically expressed by subclasses of glia are helping to address the question of where NG2-glia fit in the neuron-astroglial model of integrated brain function. NG2-glia, as well as astrocytes, have been shown to respond to neuronal and astroglial signals by raised intracellular calcium, which is a potential communications mechanism by which NG2-glia may be active partners in neuron-glial circuits. Moreover, a current concept of NG2-glia considers them to be 'neural stem cells' and an exciting prospect is that neuron-glial signalling may regulate the differentiation capacity of NG2-glia and their response to injury.     

Oligodendrocyte precursor cells: reactive cells that inhibit axon growth and regeneration

Oligodendrocyte precursor cells (OPCs) are a newly recognized glial component of the adult central nervous system of unknown function. Antibodies against the NG2 chondroitin sulfate proteoglycan have been useful tools to identify these cells in intact tissue. Here we review studies that show that OPCs react to several types of experimentally induced brain injury. Injury stimulates OPCs to re-enter the cell cycle, divide, and accumulate at the site of damage. OPCs, together with microglia and astrocytes, form the glial scar. Glial scars are thought to inhibit or prevent axonal regeneration and reactive OPCs contribute to this inhibition by producing growth-inhibiting chondroitin sulfate proteoglycans, particularly NG2. In developing animals, NG2 is found in areas, such as the perinotochordal mesenchyme, that are avoided by growing motor and sensory axons. Within the developing CNS, NG2-expressing cells surround the developing optic chiasm and tract and separate it from the overlying diencephalon. Thus, NG2-expressing cells are well positioned to inhibit axonal growth from developing as well as regenerating neurons.     

Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells

Cells that express the NG2 proteoglycan (NG2+ cells) comprise a unique population of glial cells in the central nervous system. While there is no question that some NG2+ cells differentiate into oligodendrocytes during development, the persistence of numerous NG2+ cells in the mature CNS has raised questions about their identity, relation to other CNS cell types, and functions besides their progenitor role. NG2+ cells also express the alpha receptor for platelet-derived growth factor (PDGF R), a receptor that mediates oligodendrocyte progenitor proliferation during development. Antigenically, NG2+ cells are distinct from fibrous and protoplasmic astrocytes, resting microglia, and mature oligodendrocytes. Therefore, we propose the term polydendrocytesto refer to all NG2-expressing glial cells in the CNS parenchyma. This distinguishes them from the classical glial cell types and identifies them as the fourth major glial population in the CNS. Recent observations suggest that polydendrocytes are complex cells that physically and functionally interact with other cell types in the CNS. Committed oligodendrocyte progenitor cells arise from restricted foci in the ventral ventricular zone in both spinal cord and brain. It remains to be clarified whether there are multiple sources of oligodendrocytes, and if so whether polydendrocytes (NG2+ cells) represent progenitor cells of all oligodendrocyte lineages. Proliferation of NG2+ cells during early development appears to be dependent on PDGF, but the regulatory mechanisms that govern NG2+ cell proliferation in the mature CNS remain unknown. Pulse-chase labeling with bromodeoxyuridine indicates that polydendrocytes that proliferate in the postnatal spinal cord differentiate into oligodendrocytes. Novel experimental approaches are being developed to further elucidate the functional properties and differentiation potential of polydendrocytes.     

Synantocytes: the fifth element

Classic studies have recognized neurons and three glial elements in the central nervous system (CNS) - astrocytes, oligodendrocytes and microglia. The identification of novel glia that specifically express the NG2 chondroitin sulphate proteoglycan (CSPG) raises the possibility of a fifth element. Until recently, all NG2-expressing glia were considered to be oligodendrocyte precursor cells (OPCs) that persist in the adult CNS to generate oligodendrocytes throughout life. However, this narrow view of the function of 'NG2-glia' is being challenged. The majority of NG2-expressing glia in the adult CNS are a distinct class of cells that we have called 'synantocytes' (from the Greek synanto for contact). Synantocytes are stellate cells, with large process arborizations, and are exquisitely related to neurons. Individual cells traverse white and grey matter and form multiple contacts with neurons, astrocytes, oligodendrocytes and myelin. Synantocytes are an integral component of the 'tetrapartite' synapse, and provide a potential integrative neuron-glial communications pathway. Neuronal activity, glutamate and adenosine triphosphate (ATP) act on synantocyte receptors and evoke raised intracellular calcium. It remains to be seen whether this serves a physiological function, but synantocytes may be specialized to monitor signals from neurons and glia, and to respond to changes in the integrity of the CNS via their specific contacts and ion channel and receptor profiles. The general consequences of synantocyte activation are proliferation and phenotypic changes, resulting in glial scar formation, or regeneration of oligodendrocytes, and possibly neurons.     

NG2 precursor cells in neoplasia: functional, histogenesis and therapeutic implications for malignant brain tumours

Diffusely infiltrating astrocytic tumours of the central nervous system (CNS) are the most frequent intracranial neoplasms and account for more than 60% of all primary brain tumours in man. Until recently, it was generally accepted that the glial component of the mature CNS, consisted of differentiated astrocytes, ependymal cells, oligodendrocytes and the non-neuro-ectodermal microglial cells. There exists a recently recognised population of glial cells that express the NG2 proteoglycan (NG2 cells). NG2 cells are dynamic and undergo rapid morphological changes in response to a variety of CNS pathologies. They are highly motile cells, which interact with various extracellular matrix (ECM) in association with the integrin receptors. During angiogenesis and response to tissue injury, NG2 precursor cells are recruited to sites where vessel growth and repair are occurring. NG2 is over-expressed by both tumour cells and pericytes on the blood vessels of malignant brain tumours. The function of NG2 cells in the CNS, and the notion of them as a source of and/or lineage marker for some gliomas are discussed. In addition, their possible role in glioma angiogenesis, proliferation and invasion will be considered as will their value in provision of targets for clinical and pre-clinical therapeutic strategies in brain tumours.     

Fate of neuron-glia synapses during proliferation and differentiation of NG2 cells

Progenitor cells expressing proteoglycan NG2 (also known as oligodendrocyte precursor cells or polydendrocytes) are widespread in the grey and white matter of the CNS; they comprise 8-9% of the total cell population in adult white matter, and 2-3% of total cells in adult grey matter. NG2 cells have a complex stellate morphology, with highly branched processes that may extend more than 100 μm around the cell body. NG2 cells express a complex set of voltage-gated channels, AMPA/kainate and/or γ-aminobutyric acid (GABA)(A) receptors, and receive glutamatergic and/or GABAergic synaptic input from neurons. In every region of the brain NG2 cells are found as proliferative cells, and the fraction of actively cycling NG2 cells is quite high in young as well as in adult animals. During development NG2 cells either differentiate into myelinating oligodendrocytes (and possibly also few astrocytes and neurons) or persist in the brain parenchyma as NG2 cells. This review highlights new findings related to the morphological and electrophysiological changes of NG2 cells, and the fate of synaptic input between neurons and NG2 cells during proliferation and differentiation of these cells in the neonatal and adult nervous system of rodents.     

Astrocytes and NG2‐glia: what's in a name?

Classic studies recognize two functionally segregated macroglial cell types in the central nervous system (CNS), namely astrocytes and oligodendrocytes. A third macroglial cell type has now been identified by its specific expression of the NG2 chondroitin sulphate proteoglycan (NG2-glia). These NG2-glia exist abundantly in both grey and white matter of the mature CNS and are almost as numerous as astrocytes. It is well established that NG2-glia give rise to oligodendrocytes. However, the majority of NG2-glia in the adult CNS proliferate very slowly and are non-motile. Both astrocytes and NG2-glia display a stellate morphology and express ion channels and receptors to neurotransmitters used by neurons. Both types of glia make intimate contacts with neurons in grey and white matter, and their functional differences and similarities are only beginning to be unravelled. Recent observations emphasize the need to examine the relationship between astrocytes and NG2-glia, and address the question of whether they represent overlapping or two distinct glial cell populations. To be of any relevance, this classification must relate to specific functions in the neural network. At present, the balance of evidence is that NG2-glia and astrocytes are functionally segregated populations.     

NG2-expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system

The mammalian adult central nervous system (CNS) is known to respond rapidly to demyelinating insults by regenerating oligodendrocytes for remyelination from a dividing precursor population. A widespread population of cells exists within the adult CNS that is thought to belong to the oligodendrocyte lineage, but which do not express proteins characteristic of mature myelinating oligodendrocytes, such as myelin basic protein (MBP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP). Instead, these cells have phenotypic characteristics of a more immature stage of the oligodendrocyte lineage. They express the NG2 chondroitin sulphate proteoglycan, in addition to O4 and the platelet-derived growth factor alpha-receptor, all widely accepted as markers for oligodendrocyte progenitor cells (OPCs) throughout development. However, NG2+ cells residing in the adult CNS do not resemble embryonic or neonatal NG2+ cells in terms of their morphology or proliferation characteristics, but instead represent a unique type of glial cell that has the ability to react rapidly to CNS damage. In this review, we present the evidence that adult NG2+ cells are part of the oligodendrocyte lineage and are capable of giving rise to new oligodendrocytes under both normal and demyelinating conditions. We also review the literature that these cells may have multiple functional roles within the adult CNS, notwithstanding their primary role as OPCs.     

Phenotypic and morphological characterization of in vitro oligodendrogliogenesis

The neurosphere assay has been used to maintain neural progenitor cells (NPCs) in the undifferentiated state. These cells are multipotent and gave rise to neurons and glial cells. Here we show that within 10 days of culture, neurospheres contained precursors and differentiated progeny of all three major central nervous system (CNS) cell lineages and these occupied distinct zones. The microenvironment of the inner zone supported cell differentiation. Cells of oligodendroglial lineage generated within the neurosphere were frequently observed. Of these cells, A2B5(+) cells were homogeneously distributed in the neurospheres, NG2(+) cells preferentially occupied the outer zone and O4(+) cells were localized at the inner zone of 10 day-old neurospheres. We prevented a massive cell death of dissociated neurosphere cells seen after differentiation triggered with adhesion and fetal calf serum by adding epidermal growth factor and basic fibroblast growth factor to the culture medium. Under these conditions, less than one third of cells did not express cell specific markers, glial fibrillary acidic protein-positive astroglia represented 43.4%, NG2(+) and/or O4(+) oligodendroglia represented 24.3%, and betaIII-tubulin(+) neurons 3.1% of cells recovered after neurosphere differentiation. We present evidence that oligodendroglial cells differentiate in a stepwise process as a result of their distribution in subsets that represent distinct developmental stages according to antigenic and morphological criteria. These include oligodendrocyte progenitors, preoligodendrocytes, and oligodendrocytes. The highly complex morphology of mature oligodendrocytes was compatible with functional cells.     

Instructive niches: environmental instructions that confound NG2 proteoglycan expression and the fate-restriction of CNS progenitors

Cellullar deficits are replenished within the central nervous system (CNS) by progenitors to maintain integrity and recover function after injury. NG2 proteoglycan-expressing progenitors replenish oligodendrocyte populations, but the nature of NG2 proteoglycan may not indicate a restricted population of progenitors. After injury, restorative spatiotemporal cues have the potential ability to regulate divergent fate-choices for NG2 progenitors, and NG2 progenitors are known to produce multiple cell types in vitro. Recent data suggest that NG2 expression is attenuated while protein levels remain high within injurious tissue; thus, NG2 expression is not static but transiently controlled in response to a dynamic interplay of environmental cues. Therefore, NG2 proteoglycan expression could label newly generated cells or be inherited by resident cell populations that produce oligodendrocytes for remyelination, astrocytes that provide trophic support and other cells that contribute to CNS function.