星形胶质细胞在神经系统疾病中的作用

激活的星形胶质细胞会产生和释放的神经递质、神经营养因子和促炎因子等,对神经元既有保护作用,也有毒性作用,在阿尔茨海默病、帕金森症、癫痫、缺血性脑损伤等多种神经系统疾病的发生发展过程中有着重要作用。对近年来国内外有关星形胶质细胞参与神经系统疾病进程的最新研究进展作了综述,并对今后研究工作进行了展望。     

胶质瘢痕对神经系统损伤的保护作用

胶质瘢痕是神经系统损伤后由反应性星形胶质细胞,小胶质细胞及其分泌的细胞外基质组成。早期的研究多集中于胶质瘢痕在抑制轴突生长,神经细胞再生等方面的作用。而最新的研究表明胶质瘢痕的形成对损伤急性期神经细胞具有重要的保护作用。本文从瘢痕组织在损伤缝合和组织重构、局部免疫调节、神经再生等方面对神经损伤的保护作用进行综述。     

围产期缺氧缺血性脑损伤中星形胶质细胞的病理生理改变

转产期缺氧因性脑损的研究焦点集中在神经元上,但是,星形胶持细胞也参与缺氧缺血过程并起着关键作用。星形胶质细胞在缺氧缺血损伤中的改变是中枢神经系统中最早和最显著的,这种参与对缺氧缺血变为以及中枢神经系统是损伤还是修复这一最终发展有重要影响。目前,星形胶质细胞的作用越来越受到重视,对脑缺氧缺血过程中星形胶质细胞的病理生理变化也有了深入的研究。     

星形胶质细胞

目录一、星形胶质细胞的生物学特性(一 )星形胶质细胞的异质性(二 )胶质网络二、星形胶质细胞的功能(一 )分泌功能(二 )星形胶质细胞与神经的发育及再生(三 )星形胶质细胞具有对神经元微环境调控的能力(四 )免疫功能与血脑屏障调控三、星形胶质细胞功能的新近进展(一 )星形胶质细胞也具有可兴奋性(二 )星形胶质细胞与神经元的通讯或对话(三 )在突触形成和突触可塑性中的作用(四 )星形胶质细胞与神经发生胶质细胞是神经系统内数量众多的一大类细胞群体 ,约占中枢神经系统 (CNS)细胞总数的 90 % ,星形胶质细胞 (astrocyte)是其中主要的组成…     

发育中星形胶质细胞兴奋在惊厥中的作用

惊厥是神经系统最常见的症状之一,发育中脑惊厥可以影响远期惊厥易感性、学习和记忆等功能。星形胶质细胞兴奋是近来才发现的新特性,此种特性参与了惊厥性脑损伤这一复杂病理过程。对于发育中星形胶质细胞兴奋在惊厥性脑损伤中作用的研究,可以阐明星形胶质细胞兴奋与神经元在惊厥中的相互关系,并了解它们在发育中兴奋毒性损伤中的作用及其量效关系,这些研究结果将有可能对抗惊厥的治疗提供新的靶点,对于进一步了解发育中惊厥性损伤远期预后的发生机制具有重要意义,可以为早期干预提供理论依据。     

疼痛研究的新亮点:星形胶质细胞

一直以来疼痛被认为仅仅是由神经元调节的。目前的研究表明,星形胶质细胞与疼痛有密切的关系。星形胶质细胞通过许多重要功能如参与信号转导、被激活而表现出激活的特性,如释放促炎性因子、神经营养因子等,在疼痛调节过程中发挥重要作用。对星形胶质细胞与疼痛关系的研究,必将为疼痛机制的阐明及疼痛治疗提供新的思路。     

正加速度暴露对大鼠海马星形胶质细胞GFAP表达的影响

目的探讨正加速度( Gz)重复暴露后不同时间海马星形胶质细胞GFAP表达的变化.方法 SD大鼠60只,随机分成对照组、 Gz重复暴露后1h、6h、12h、24h和48h组,每组10只.采用动物离心机,建立 Gz引发急性脑缺血模型;应用免疫组织化学技术,分别检测 Gz重复暴露后不同时间,海马星形胶质细胞GFAP的表达状况.结果海马星形胶质细胞GFAP阳性细胞数,在 Gz暴露后1h即显著增加,于12h达到高峰,而后逐渐下降,48h仍维持在较高水平,实验组与对照组比较,有显著性差异.结论 Gz重复暴露导致海马星形胶质细胞GFAP表达上调,可能对神经元的缺血损伤起保护作用.     

小胶质细胞和星形胶质细胞相互作用在中枢神经系统疾病中的作用机制研究进展

小胶质细胞和星形胶质细胞是中枢神经系统主要的两种胶质细胞,两者各自在中枢神经系统中扮演着重要的角色。本文主要从小胶质细胞和星形胶质细胞相互交流这一新的角度,概述两种胶质细胞相互作用方式及在中枢神经系统中的研究现状,并进一步阐明两者相互作用在各种中枢神经系统疾病的功能及机制,旨在为进一步了解这两种胶质细胞在中枢神经系统疾病的作用机理提供理论依据、为治疗相关中枢系统疾病提供新思路。     

星形胶质细胞功能障碍在抑郁症发病中的作用研究进展

星型胶质细胞在突触形成、神经元代谢、神经递质传递等方面起重要作用,其退行性病变可引起突触蛋白水平降低、神经元体积减小及神经递质传递异常,进而引起神经精神性疾病的发生。抑郁症患者前额叶皮层、海马、杏仁核以及前扣带回等多个脑区均有星型胶质细胞密度减低,提示星形胶质细胞与抑郁症发病密切相关。研究表明,能量和营养支持、谷氨酸(glutamate,Glu)转运和代谢、N-甲基-D-天(门)冬氨酸(N-methyl-D-aspartate,NMDA)受体活性调节以及炎症反应异常等星形胶质细胞功能障碍参与抑郁症的发生。本文就星形胶质细胞功能障碍在抑郁症发病机理中的作用进行综述。     

Effective delivery of antisense peptide nucleic acid oligomers into cells by anthrax protective antigen

Peptide nucleic acid (PNA) is highly stable and binds to complementary RNA and DNA with high affinity, but it resists cellular uptake, thereby limiting its bioavailability. We investigated whether protectiveantigen (PA, a non-toxic component of anthrax toxin) could transport antisense PNA oligomers into reporter cells that contain luciferase transgenes with mutant β-globin IVS2 intronic inserts, which permit aberrant pre-mRNA splicing and impair luciferase expression. PNA oligomers antisense to mutant splice sites in these IVS2 inserts induced luciferase expression when effectively delivered into the cells. PNA 18-mers with C-terminal poly-lysine tails [PNA(Lys)₈] demonstrated modest sequence-specific antisense activity by themselves at micromolar concentrations in luc-IVS2 reporter cell cultures. However, this activity was greatly amplified by PA. Antisense PNA(Lys)₈ with but not without PA also corrected the IVS2-654 β-globin splice defect in cultured erythroid precursor cells from a patient with β-thalassemia [genotype, IVS2-654(β⁰/β^E)], providing further evidence that anthrax PA can effectively transport antisense PNA oligomers into cells.     

The effects of running activity on the reproductive axes of rodents

Access to a running wheel causes gonadal recrudescence in Syrian hamsters whose reproductive axes have been suppressed by housing them under short day lengths (Borer et al. 1983). The first experiment tested the generality of this phenomenon in a population of rodents that is genetically heterogeneous for reproductive photoresponsiveness. Male meadow voles (Microtus pennsylvanicus) of the two extreme phenotypes — reproductively photoresponsive and non-responsive — were either provided with a running wheel or housed without one. After 4 weeks with a wheel, the responsive voles had recovered full reproductive function, while the reproductive axes of responsive voles housed without wheels remained suppressed. Three experiments queried whether the use of a wheel would have reproductively stimulative effects in other rodents. First, intact male mice given access to wheels showed no increase in testis size when compared to mice housed without wheels. Likewise, locomotor activity had no effect on male rats whose testes were partially regressed in response to testosterone implants or on female mice whose estrous cycles were pheromonally suppressed by housing them in groups. Thus the neuroendocrine pathway used by locomotor activity to enhance the secretion of gonadotropin is specifically allied with the pathway used by photoperiod to control GnRH secretion.Abbreviations GnRH gonadotropin-releasing hormone - LH luteinizing hormone     

Entamoeba histolytica: intracellular distribution of the sec61alpha subunit of the secretory pathway and down-regulation by antisense peptide nucleic acids

The Sec61alpha protein is defined as a highly conserved essential integral component of the endoplasmic reticulum in eukaryotic cells. We report a detailed immunolocalization of the Entamoeba histolytica homologue of the Sec61alpha subunit (EhSec61alpha), which shows an irregular pattern throughout the cell and is also found on the cell surface, its effective down-regulation by means of antisense peptide nucleic acids and its effects on cell proliferation, subcellular distribution of two virulence factors, and the ability of the trophozoites to cause liver abscess in hamsters. Although Sec61alpha levels are specifically decreased in antisense PNA-treated trophozoites, which proliferate more slowly than the controls, mobilization of the cysteine protease 5 and amoebapore to the cell surface is not significantly impeded and the capacity to induce liver abscess in hamsters is largely unaffected. The implications of these findings are discussed in the context of the peculiar cell biology of E. histolytica.     

Hoxb-5 control of early airway formation during branching morphogenesis in the developing mouse lung

Hox proteins control structural morphogenesis, pattern formation and cell fate in the developing embryo. To determine if Hoxb-5 participates in patterning of early airway branching during lung morphogenesis, gestational day 11.5 embryonic lung cultures were treated with retinoic acid (RA) to up-regulate and antisense oligonucleotides to down-regulate Hoxb-5 protein expression. RA (10^?6 M) and Hoxb-5 antisense oligonucleotide (20 μM) treatment each significantly decreased branching morphogenesis (P<0.001), but the morphology of branching under these conditions was very different. RA-treated lungs had elongated primary branches but decreased further branching with increased Hoxb-5 immunostaining in subepithelial regions underlying these elongated airways. Western blots confirmed that Hoxb-5 protein was increased by 189±20% (mean±S.E.M., P<0.05) in RA-treated lungs compared to controls. In contrast, lungs treated with Hoxb-5 antisense oligos plus RA had foreshortened primary branches with rudimentary distal clefts resulting in decreased numbers of primary and subsequent branches. Immunohistochemistry confirmed that Hoxb-5 antisense oligos inhibited Hoxb-5 protein expression even in the presence of RA. We conclude that regional and quantitative changes in Hoxb-5 protein expression influence morphogenesis of the first airway divisions from the mainstem bronchi. RA-induced alterations in branching are mediated in part through regulated Hoxb-5 expression.     

Prediction of VEGF mRNA antisense oligodeoxynucleotides by RNA structure software and their effects on HL60 and K562 cells

Seven antisense oligodeoxynucleotides were selected using RNA structure 3.7 software and the principle of low overall DeltaG (free energy). Their effects on cell growth, VEGF protein expression and apoptosis in HL60 and K562 leukemic cells were examined, and cell numbers and viability were assessed using trypan blue dye exclusion, MTT, ELISA and flow cytometry. The results showed that six of the seven antisense sequences inhibited the cell growth and down-regulated VEGF protein expression significantly. Endogenous VEGF plays an important role in the proliferation of HL60 and K562 leukemic cells. RNA structure software provides a rapid and efficient way of identifying effective antisense oligodeoxynucleotides.     

Composition,synthetic and cytolytic activities of Galleria mellonella silk glands during the last-larval instar under the action of juvenile hormone

Within the first 48 hr of the last-larval instar of Galleria mellonella the silk glands grow but silk production is restrained. This ‘preparatory phase’ of the glands is probably maintained by juvenile hormone. Silk production and accumulation are stimulated in the ‘accumulation phase’ between 60 and 132 hr by unknown factors in the absence of juvenile hormone. The rate of RNA synthesis culminates at 84 hr but the RNA content increases until the end of cocoon spinning at 144 hr. In the following ‘regression phase’ (144–160 hr), when the glands exhibit high activities of acid and alkaline DN-ases and of acid phosphatase, the RNA and protein contents rapidly decrease, but that of DNA remains high. This phase is typical of moulting insects, is independent of juvenile hormone, and seems to be caused either by an increase in ecdysteroids or by lack of nutrients. The following ‘degeneration phase’ occurs when the surge of ecdysteroids terminates the larval-pupal transformation. Disintegration of silk glands by autolysis and phagocytosis is completed after pupal ecdysis (180 hr). Treatment of larvae with a juvenoid (ZR 512) at 48 or 132 hr in the last instar dramatically alter the composition, synthetic and cytolytic activities of silk glands. At the next ecdysis the glands attain a state very similar to that of the preparatory phase. They are capable of intensive silk production and completion of developmental cycle when the supernumerary larvae prepare for pupation. The results indicate that juvenile hormone can reverse the development of the silk glands.     

Estimating the number of plasmids taken up by a eukaryotic cell during transfection and evidence that antisense RNA abolishes gene expression in Physarum polycephalum

We have estimated the statistical distribution of the number of plasmids taken up by individual Jurkat lymphoma cells during electroporation in the presence of two plasmids, one encoding for yellow (EYFP) the other for cyan (ECFP) fluorescent protein. The plasmid concentration at which most of the cells take up only one plasmid or several molecules was determined by statistical analysis. We found that cells behaved slightly heterogeneous in plasmid uptake and describe how the homogeneity of a cell population can be quantified by Poisson statistics in order to identify experimental conditions that yield homogeneously transfection-competent cell populations. The experimental procedure worked out with Jurkat cells was applied to assay the effectiveness of antisense RNA in knocking down gene expression in Physarum polycephalum. Double transfection of flagellates with vectors encoding EYFP and antisense-EYFP revealed for the first time that gene expression can be suppressed by co-expression of antisense RNA in Physarum. Quantitative analysis revealed that one copy of antisense expressing gene per EYFP gene was sufficient to completely suppress formation of the EYFP protein in Physarum.     

Enhancing effects of heat shock and gibberellic acid on the thermotolerance in etiolated Vigna radiata. I. Physiological aspects on thermotolerance

The effect of heat shock on the thermotolerance of etiolated mung bean seedlings ( Vigna radiata L. cv. Wilczek) and the effects of gibberellic acid (GA) were studied. The potentially lethal temperature of etiolated mung bean seedlings was 45°C. But, when seedlings were pretreated with a heat-shock period at 40°C for 1 h before incubation at 45°C, they become thermotolerant and survived the 45°C treatment. The addition of actinomycin D or cycloheximide during the heat-shock period decreased the subsequent thermotolerance of the seedlings. Depending upon the time of its application, GA appeared to have multiple effects: (1) when applied during the 40°C heat-shock period, GA enhanced the heat-shock effect; (2) when applied during the 45°C potentially lethal temperature period, GA enhanced the subsequent growth of hypocotyls. This suggests that GA makes the seedlings tolerant to the potentially lethal temperature; (3) when GA was applied during a following 25°C growth period to seedlings which had been exposed first to 40°C and then 45°C, it promoted growth, suggesting that GA enhanced the restoration of the seedlings from high temperature damage. The role of GA and heat shock in the acquisition of thermotolerance in etiolated mung bean seedlings are discussed.     

Changes in the metabolism of glial fibrillary acid protein (GFAP) during chronic relapsing experimental allergic encephalomyelitis in the strain 13 guinea-pig

Spinal cords were removed from strain 13 guinea pigs in various stages of chronic relapsing experimental allergic encephalomyelitis (CREAE). Levels of glial fibrillary acidic protein (GFAP) in cord extracts were determined by radioimmunoassay and protein synthesis was monitored by incubating tissue prisms with [³⁵S]methionine. Analysis of cytoskeletal enriched preparations from these incubations by SDS-polyacrylamide electrophoresis and fluorography permitted evaluation of the metabolism of discrete polypeptides; the identity of a labelled band at 51,000 daltons as GFAP was confirmed by immunoprecipitation with a specific antibody. Total protein synthesis increased 4-fold during the acute phase of CREAE but fell to control values with clinical recovery, while over the same period GFAP synthesis increased by 6–7-fold and remained elevated in the post-acute phase at about 200% of control values. During this time there was no increase in the GFAP content of the cord indicating an increased turnover of this protein rather than net synthesis. In later stages of CREAE however, GFAP levels were raised, correlating with a further increase in the incorporation of precursor into GFAP, this being most pronounced in animals in clinical relapse.