胶质细胞介导性激素的神经系统作用

性激素在神经系统的作用包括调节突触可塑性,参与脑的性别分化,衰老过程和神经损伤修复等,胶质细胞表达性激素受体,是性激素的靶细胞,性激素通过对胶质细胞的作用,再影响神经系统的功能,胶质细胞成为性激素对神经系统作用的中间环节。     

多巴胺能神经细胞损伤过程中NCAM-140的表达变化

目的:检测NCAM.140在多巴胺能神经细胞损伤过程中中脑黑质部位的表达变化,探索其在多巴胺能神经细胞损伤中的可能作用.方法:采用MPTP腹腔注射建立小鼠中脑黑质多巴胺能神经细胞慢性损伤模型,采用免疫荧光染色和westernblotting检测中脑黑质部酪氨酸羟化酶(TH)和NCAM-140的表达情况.结果:在小鼠中脑黑质一直有NCAM-140阳性细胞存在,且与TH阳性细胞共表达;TH在给予MPTP后第三周表达开始降低,NCAM-140在给予MPTP后第一周至第三周持续高表达,并且从第四周开始,其表达量明显降低.结论:NCAM-140的表达与多巴胺能神经细胞损伤有关.     

神经细胞粘附分子与硫酸化氨基聚糖在神经发育、轴突生长、突触可塑性及学习和记忆中的作用

神经细胞粘附分子（neural cell adhesion molecule,NCAM)是一种主要表达于神经系统的糖蛋白,通过亲同性及亲异性结合介导细胞与细胞与细胞外基质间的相互作用,参与细胞的识别,迁移,轴突生长,细胞信号转导,学习和记忆等过程。硫酸化氨基聚糖可调节脑发育中的细胞分化,轴突生长及中枢神经系统中神经元的再生,可能参与了与学习和记忆相关的神经结构功能的调节。这些作用可能与神经细胞粘附分子的亲异性结合有关。     

Tenascin-r基因在斑马鱼胚胎发育中时空表达规律

Tenascin-r(TNR)是一种脊椎动物细胞外基质糖蛋白,在不同的物种间具有高度保守性,主要表达于神经系统,通过调节基质粘附状态和基质间相互作用而促进细胞的迁移、增殖和分化.在小鼠等动物模型中,TNR在中枢神经系统的发育中起重要作用,能控制大脑活动、调节适应性行为.而在斑马鱼研究中,TNR仅在视神经的发育和修复中起作用,通过对TNR在斑马鱼胚胎发育时期时空表达规律的研究,可以为利用斑马鱼进一步研究TNR的功能建立一个平台.     

神经粘附分子CHL1在神经系统中的研究进展

粘附分子通过介导细胞间相互作用发挥其在发育、再生和突触修饰等方面的重要作用.神经细胞粘附分子CHL1(close homologue of L1)是近年发现的粘附分子,属于粘附分子免疫球蛋白超家族,集中表达于神经系统,通过亲异性作用(heterophilic interaction)介导细胞与细胞、细胞与胞外基质的相互作用,进而参与神经系统的发育、轴突的生长、迁移及导向等过程.     

转化生长因子β1在脑积水发生中的作用

脑积水是以脑脊液流动障碍和脑萎缩为主要特点的神经系统疾病.遗传突变、先天性畸形、感染、颅内出血和肿瘤等均能导致不同程度的脑积水.转化生长因子β1(TGF-β1)是脑发育过程中一种重要的生长因子,该基因过表达小鼠可通过调节基质金属蛋白酶-9和基质金属蛋白酶组织抑制剂-1的表达,改变细胞外基质环境,从而导致脑积水形成.本文就TGF-β1在脑积水发生中的作用做一综述.     

神经系统中的肿瘤抑制因子PTEN

PTEN是定位于10q23的第一个具有磷酸酶活性的抑癌基因,它能通过PI3K/AKT、FAK和MAPK信号转导通路调节细胞的生长、凋亡、迁移和转化。PTEN在神经系统的神经元中有广泛表达,其在调节神经干细胞的增殖、SVZ前体细胞的迁移及凋亡、PC12细胞的分化和神经突触的建立方面具有重要作用。因此,对PTEN功能的进一步研究将为肿瘤和神经性疾病的治疗提供新的思路。     

FHFs在心律失常中作用及机制的研究进展

成纤维细胞生长因子同源性因子(fibroblast growth factor homologous factors,FHFs)作为一类特殊的成纤维细胞生长因子,因发现其不能分泌到细胞外且可以调节电压依赖性钠通道而倍受关注,先前的研究发现FHFs对神经系统具有重要影响并与多种神经系统疾病有关,最近的研究证明FHFs在心脏中也具有重要作用并可能与某些心律失常的发生相关。本文将通过综述FHFs在蛋白结构、心肌中的表达、对心肌钠、钙通道蛋白的调节、对心肌兴奋性和传导性的影响等方面来重点阐述FHFs在心律失常中的作用及其机制。     

活化的T细胞核内因子（NFAT）的调节及其在神经系统中的功能

活化的T细胞核内因子（nuclear factor of activated T-cells, NFAT）作为细胞信号转导通路中的一类重要的转录因子参与细胞功能的调节. NFAT的活化主要是通过细胞内钙/钙调神经磷酸酶（Ca2+/calcineurin）的刺激启动,它脱磷酸后发生核转位并与DNA的特定序列结合,同时通过与其它转录因子的协同作用,调节目的基因的特定表达. NFAT在免疫系统中所调节的基因表达已经得到了充分的研究. 近年实验研究发现,NFAT的转录因子家族在脊椎动物的神经系统中也发挥着非常重要的作用. 本文综述了NFAT家族蛋白的分类、结构、磷酸酶与激酶对其出入核的调节及在神经系统中的研究进展,使得能够更加全面地认识calcineurin/NFAT信号通路的作用. 此外,由于环孢菌素A（cyclosporin A）等药物在神经系统应用的局限性,对于NFAT调节深入研究,也将为筛选或者开发更为高效、低毒药物提供新的思路.     

孕激素在自身免疫疾病中的免疫调节作用

孕激素是一种免疫调节分子,它主要通过与孕激素受体结合发挥免疫调节作用。大量研究证实,孕激素受体在多种淋巴细胞表达,孕激素在免疫调节中可诱导Th2细胞反应,抑制Th1细胞反应,抑制巨噬-单核细胞、自然杀伤细胞的杀伤活力。血清孕激素水平降低,孕激素受体表达调节障碍将影响自身免疫功能的调节,导致自身免疫性疾病的发生和发展。     

Up-regulation of embryonic NCAM in an EC cell line by retinoic acid

The impact of retinoic acid (RA) on the expression of the neural cell adhesion molecules (NCAMs) and their developmentally regulated polysialic acid (PSA) moiety was studied in embryonal carcinoma (EC) cell lines. These cell lines are known to be capable of RA-induced differentiation into neurons (murine P19 cells) or parietal endoderm (murine F9 cells), respectively. Monoclonal antibodies were employed to monitor expression of NCAM and PSA. F9 and P19 cells were both found to express NCAM but only P19 cells carried the highly polysialylated "embryonic form" of NCAM (E-NCAM). The amount of NCAM in aggregated P19 cells but not in F9 cells was dramatically increased upon treatment with RA. Since NCAMs play an important role in cell interactions during embryogenesis it is tempting to speculate that the regulative impact of RA on NCAMs is related to its morphogenic property.     

NCAM Function in the Adult Brain: Lessons from Mimetic Peptides and Therapeutic Potential

Neural cell adhesion molecules (NCAMs) are complexes of transmembranal proteins critical for cell–cell interactions. Initially recognized as key players in the orchestration of developmental processes involving cell migration, cell survival, axon guidance, and synaptic targeting, they have been shown to retain these functions in the mature adult brain, in relation to plastic processes and cognitive abilities. NCAMs are able to interact among themselves (homophilic binding) as well as with other molecules (heterophilic binding). Furthermore, they are the sole molecule of the central nervous system undergoing polysialylation. Most interestingly polysialylated and non-polysialylated NCAMs display opposite properties. The precise contributions each of these characteristics brings in the regulations of synaptic and cellular plasticity in relation to cognitive processes in the adult brain are not yet fully understood. With the aim of deciphering the specific involvement of each interaction, recent developments led to the generation of NCAM mimetic peptides that recapitulate identified binding properties of NCAM. The present review focuses on the information such advances have provided in the understanding of NCAM contribution to cognitive function.     

Fundamental Characteristics of Neuron Adhesion Revealed by Forced Peeling and Time-Dependent Healing

A current bottleneck in the advance of neurophysics is the lack of reliable methods to quantitatively measure the interactions between neural cells and their microenvironment. Here, we present an experimental technique to probe the fundamental characteristics of neuron adhesion through repeated peeling of well-developed neurite branches on a substrate with an atomic force microscopy cantilever. At the same time, a total internal reflection fluorescence microscope is also used to monitor the activities of neural cell adhesion molecules (NCAMs) during detaching. It was found that NCAMs aggregate into clusters at the neurite-substrate interface, resulting in strong local attachment with an adhesion energy of ∼0.1 mJ/m² and sudden force jumps in the recorded force-displacement curve. Furthermore, by introducing a healing period between two forced peelings, we showed that stable neurite-substrate attachment can be re-established in 2–5 min. These findings are rationalized by a stochastic model, accounting for the breakage and rebinding of NCAM-based molecular bonds along the interface, and provide new insights into the mechanics of neuron adhesion as well as many related biological processes including axon outgrowth and nerve regeneration.     

Expression of neural cell adhesion molecules,NCAMs, and their polysialylated forms,PSA-NCAMs,in the developing rat pituitary gland

Neural cell adhesion molecules (NCAMs) can undergo post-translational modifications, such as the addition of polysialic acid chains, thus generating PSANCAMs, which are expressed mainly during development. Since polysialylation considerably modifies NCAM adhesivity, expression of NCAMs and PSANCAMs has been investigated in the developing hypophysis by immunohistochemistry. At embryonic day 13 (E13), an antibody against NCAM outlined all cellular profiles in the entire Rathke's pouch; this labelling persisted until adulthood. NCAM expression increased in all lobes during development and concerned all pituitary cell types. In contrast, at E13, PSA-NCAMs were only detected in the neural lobe, solely constituted of pituicytes at this stage, and the tuberal lobe, the only lobe expressing hormonal mRNA at the same stage. PSA-NCAMs expression increased in the neural lobe at E17 with the arrival of the neurosecretory fibres and persisted into adulthood. In the anterior lobe, PSA-NCAMs appeared at E15 where their distribution was similar to that of the differentiating corticotrophic cells; at subsequent stages, their expression extended to the whole anterior lobe. Only two cell types, corticotrophic and somatotrophic cells, remained labelled in the adult gland. In the intermediate lobe, melanotrophic cells never expressed PSA-NCAMs but these were expressed on folliculo-stellate cells at birth, preceding the onset of innervation. These results suggest that NCAMs and PSA-NCAMs play a role in pituitary histogenesis, cell differentiation and neurointermediate lobe innervation.     

Structural basis for the activation of FGFR by NCAM

The fibroblast growth factor receptor (FGFR) can be activated through direct interaction with the neural cell adhesion molecule (NCAM). The extracellular part of the FGFR consists of three immunoglobulin-like (Ig) modules, and that of the NCAM consists of five Ig and two fibronectin type III (F3) modules. NCAM-FGFR interactions are mediated by the third FGFR Ig module and the second NCAM F3 module. Using surface plasmon resonance and nuclear magnetic resonance analyses, the present study demonstrates that the second Ig module of FGFR also is involved in binding to the NCAM. The second Ig module residues involved in binding were identified and shown to be localized on the "opposite sides" of the module, indicating that when NCAMs are clustered (e.g., due to homophilic binding), high-affinity FGFR binding sites may be formed by the neighboring NCAMs.     

Immunohistochemical and biochemical analyses of GD3, GT1b,and GQ1b gangliosides during neural differentiation of P19 EC cells

In an earlier study, we showed that expressions of GD3, GT1b, and GQ1b gangliosides in P19 embryonic carcinoma (EC) cells were enhanced during their neural differentiation induced by retinoic acid. We now further demonstrated that this increase of the b-series gangliosides is due to an increase in their corresponding synthases (sialyltransferase-II, -IV, and -V) in the Golgi. Of the three gangliosides studied, GQ1b appeared to be the best candidate for monitoring such differentiation process. We also used fluorescence-labeled monoclonal antibodies and confocal fluorescence microscopy to obtain direct visual information about the relationship of gangliosides and neural specific proteins in neuron development. Again, GQ1b is the most interesting as it localizes with synaptophysin and neural cell adhesion molecules (NCAMs) on synaptic boutons or dendritic spines in RA-induced neurons (R/N). This suggests that GQ1b could be used as a marker for synapse formation during construction of the neural network.     

Sexual selection and intelligence: Does sexual reproduction drive the evolution of intelligence?

The basal hypothesis discussed here is the idea that brain architecture could be plastic on a very basal, genetic level due to sexual recombination and reassortment of alleles of genes related to brain development, e.g., neuronal cell adhesion molecules (NCAMs) and others.The role of sexual reassortment leads the study of brain development, species behavior and intelligence to a new version of the so-called “Red Queen Hypothesis”: using the mechanism described here, a kind of runaway selection mechanism seems to arise. Even if NCAMs are almost constant within an individual, they seem to act very differently at the population level and so the role of reassorting polymorphic NCAM- (and other) genes gets particularly clear. If several NCAM-NCAM combinations cause extreme behavior and intelligence variability in a population, these combinations also represent a use of sexual selection. This mechanism of NCAM allele assortment seems to be important for the process of speciation by mutual selection of individuals. Therefore NCAM variants and their associated behaviors are thought to be important for the development of intelligence, in that they promote the attraction of individuals with already high intelligence, leading to the speciation of super-intelligent groups.     

Palladin regulation of the actin structures needed for cancer invasion

Cell migration and invasion involve the formation of cell adhesion structures as well as the dynamic and spatial regulation of the cytoskeleton. The adhesive structures known as podosomes and invadopodia share a common role in cell motility, adhesion, and invasion, and form when the plasma membrane of motile cells undergoes highly regulated protrusions. Palladin, a molecular scaffold, co-localizes with actin-rich structures where it plays a role in their assembly and maintenance in a wide variety of cell lines. Palladin regulates actin cytoskeleton organization as well as cell adhesion formation. Moreover, palladin contributes to the invasive nature of cancer metastatic cells by regulating invadopodia formation. Palladin seems to regulate podosome and invodopodia formation through Rho GTPases, which are known as key players in coordinating the cellular responses required for cell migration and metastasis.     

Palladin regulation of the actin structures needed for cancer invasion

Cell migration and invasion involve the formation of cell adhesion structures as well as the dynamic and spatial regulation of the cytoskeleton. The adhesive structures known as podosomes and invadopodia share a common role in cell motility, adhesion, and invasion, and form when the plasma membrane of motile cells undergoes highly regulated protrusions. Palladin, a molecular scaffold, co-localizes with actin-rich structures where it plays a role in their assembly and maintenance in a wide variety of cell lines. Palladin regulates actin cytoskeleton organization as well as cell adhesion formation. Moreover, palladin contributes to the invasive nature of cancer metastatic cells by regulating invadopodia formation. Palladin seems to regulate podosome and invodopodia formation through Rho GTPases, which are known as key players in coordinating the cellular responses required for cell migration and metastasis.