神经胶质细胞与HIV相关神经认知障碍

HIV-1相关神经认知障碍(HIV-1 associated neurocognitive disorder,HAND)是艾滋病患者中枢神经系统(central nervous system,CNS)的常见并发症,其患病率高达40%~60%,是40岁以下成人痴呆的最主要原因之一;患者从确诊到死亡的平均时间约为4~6个月,且其发病机理尚待研究.已有的研究表明,HIV-1不感染神经元,但在HAND的发病机制中,神经胶质细胞的过度活化和由此而引发的神经炎症起着重要的作用.本文就神经胶质细胞在HAND的发生发展中的作用进展进行综述.     

星形胶质细胞与缺血性脑水肿

随着对神经系统疾病机制研究的不断深入,人们认识到,它在生理和病理下均发挥极其重要的作用.脑水肿及后继的颅内压升高和脑疝形成是脑缺血主要的并发症.星形胶质细胞可通过多种途径影响脑水肿的发生.发展以及消退.明确星形胶质细胞在缺血性脑水肿中的作用及其机制,可能将为脑缺血的治疗提供新的靶点.     

脊髓中S100b基因的表达模式研究

S100b是一种钙离子结合蛋白,与阿尔兹海默症、帕金森症、神经痛等多种神经系统疾病有关.实验通过原位杂交和免疫荧光技术对S100b在中枢神经系统的表达模式进行直接分析,发现S100b主要表达在脊髓灰质星形胶质细胞和脊髓白质中正在成熟的少突胶质细胞中,表明其并不能很好的作为星形胶质细胞的分子标记物.     

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.     

脂多糖诱导星形胶质细胞炎性反应的机制研究

目的 探讨脂多糖(LPS)诱导星形胶质细胞产生炎性反应及其可能机制.方法 原代培养并鉴定C57BL/6小鼠大脑皮质星形胶质细胞,GFAP免疫荧光染色进行鉴定,1μg/mL LPS刺激第2代星形胶质细胞,正常组细胞作为对照,Griess法检测NO的释放,ELISA检测细胞因子IL-6、IL-1β和TNF-α的水平,免疫荧...     

阿片成瘾中的神经免疫机制

综述小胶质细胞参与阿片类物质成瘾行为的细胞和分子机制,以及神经免疫抑制剂防治阿片成瘾的研究进展。阿片类物质成瘾是严重的医学和社会问题。目前针对阿片成瘾的研究主要集中在神经元,戒毒药物也主要针对阿片受体,然而其效果有限。神经元不是神经通路的唯一组分,神经小胶质细胞占中枢神经系统细胞总数的10%~15%,然而其作用和功能一度被忽视。阿片能激活Toll样受体4(TLR4),活化小胶质细胞,分泌大量炎症因子,从而调节奖赏信号通路,增加神经元兴奋性,参与成瘾行为的形成和表现。研究调节性神经免疫因子以及它们所造成神经炎症反应,将为理解阿片所造成的大脑功能改变和成瘾行为提供新的思路。     

神经生长因子对神经干细胞向少突胶质细胞分化的诱导作用研究

目的体外分离和培养大鼠海马神经前体细胞,在此基础上探索在体外环境下使神经干细胞定向分化为少突胶质细胞,为后续的神经干细胞移植提供实验基础.方法取孕10 d的Wistar大鼠胚胎脑的海马,分离神经前体细胞,将单克隆的神经干细胞球贴壁,并使用生长因子(NGF),分析不同浓度的NGF对神经干细胞分化的影响.在含NGF的NSC培养基中进行体外培养,以GalC免疫组化标记分化后的少突胶质细胞,对神经干细胞的分化特性进行鉴定.结果NGF可促进神经前体细胞的增殖及神经球的克隆形成,并获得了Nestin阳性的神经前体细胞,其可分化为分别表达GaIC的阳性细胞.结论体外分离和培养的大鼠海马神经前体细胞,在NGF生长因子的作用下,神经干细胞可定向分化为少突胶质细胞,并与培养基中NGF的浓度有一定的关系,有望应用于脱髓鞘神经系统疾病的细胞移植治疗.     

刺参多糖对星形胶质细胞活化作用机制研究

目的探讨刺参多糖对星形胶质细胞的活化作用机制.方法选取新生Wistar大鼠24只,经胰酶消化分离可得星形胶质细胞;采用MTT法检测HS-4对细胞的毒副作用;采用伊红染色与免疫荧光染色检查细胞的形态学变化;采用Western blot法检测细胞特征蛋白GFAP和细胞周期调控蛋白Cyc DI的表达;采用BrdU法检测细胞的增殖;采用Transwell法检测细胞的迁移.结果 HS-4浓度在0.1～100μg/mL,作用时间为3,5 d时,细胞数量与对照组差异不显著,HS-4浓度在100μg/mL,作用时间为7 d时,细胞存活率明显低于对照组,差异显著;体外培养的细胞与HS-4单独作用,细胞形态无明显改变,HS-4与FGF-2联合作用后,细胞形态发生明显改变;星形胶质细胞的特征蛋白GFAP表达水平显著升高,HS-4在1μg/mL和5μg/mL时,GFAP表达升高了169%和183%;对照组细胞周期调控蛋白Cyc DI表达最低,FGF-2单独作用后,Cyc DI表达略有升高,当HS-4与FGF-2联合作用后,Cyc DI表达明显升高;对照组BrdU阳性率最低,占细胞总数的12.9%,FGF-2单独作用后,BrdU阳性率略有升高,占细胞总数的16.4%,与对照组差异不显著,HS-4浓度为1μg/mL和5μg/mL时与FGF-2联合作用,BrdU阳性率明显升高,占细胞总数的28.5%和56.1%,与对照组相比差异显著;静息状态星形胶质细胞无迁移,HS-4与FGF-2作用下星形胶质细胞迁移明显.结论 HS-4与FGF-2能有效诱导星形胶质细胞的活化,其活化机制主要是强化细胞增殖与迁移.     

大鼠皮层星形胶质细胞体外培养的对比研究

比较3种不同培养星形胶质细胞的方法,以获得高纯度星形胶质细胞,为体外研究其生物学功能奠定基础.取新生SD大鼠的皮层区,应用原代培养法、差速贴壁培养法和震荡法,通过形态学观察、胶质纤维酸性蛋白(GFAP)免疫荧光染色法和台盼蓝染色法,对比分析3种不同培养方法所获得星形胶质细胞的纯度和活性.差速贴壁组星形胶质细胞纯度(98.4%)明显高于原代培养组和震荡组.经台盼蓝染色发现,各组细胞活细胞率均大于95%,表明3种培养方法对于细胞活性没有显著影响.差速贴壁培养法培养星形胶质细胞的方法具有简便可行,纯度高的优点,可作为星形胶质细胞体外培养的良好模型.     

小鼠脊髓损伤后对少突胶质细胞前体细胞发育的影响

为研究小鼠脊髓损伤后脊髓少突胶质细胞前体细胞的发育分化情况,选择基因型为PDGFRa-creER+/Rosa-tdTomato+小鼠为研究对象,用脊髓损伤仪损伤小鼠脊髓T8或T9段.伤后休养30d取材,通过免疫荧光、激光共聚焦和电镜的方法分析取样材料,发现在物理损伤30d后,大部分表达tomato阳性的细胞同时表达少突胶质细胞的标志蛋白CC1,一小部分细胞同时表达星形胶质细胞的标志蛋白GFAP.     

大学生网络成瘾成因分析及干预

高等院校是社会人才培养和知识创新的基地,成为全社会信息化程度最高的社区之一.高校学生网络成瘾问题日益凸显,严重损害了大学生的学业和身心健康.对大学生网络成瘾成因进行了深入分析,并提出干预策略:提出从学生个人方面、学生家庭方面、学校教育管理方面及社会方面等四大方面入手对学生的网络成瘾问题进行干预,做到防患于未然.     

Learning about addiction from the genome

Drug addiction can be defined as the compulsive seeking and taking of a drug despite adverse consequences. Although addiction involves many psychological and social factors, it also represents a biological process: the effects of repeated drug exposure on a vulnerable brain. The sequencing of the human and other mammalian genomes will help us to understand the biology of addiction by enabling us to identify both genes that contribute to individual risk for addiction and those through which drugs cause addiction. We illustrate this potential impact by searching a draft sequence of the human genome for genes related to desensitization of receptors that mediate the actions of drugs of abuse on the nervous system.     

Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells

Patients with certain genetic disorders can be cured by bone marrow transplantation. However, as prospective donors do not exist for most patients with potentially curable genetic abnormalities, an alternative treatment for such patients involves the transfer of cloned genes into the patient's haematopoietic stem cells followed by re-infusion of the treated cells. Retroviral vectors provide an efficient means for transferring genes into mammalian cells and have been used to transfer genes into mouse haematopoietic cells. We have now produced amphotropic retroviral vectors containing either the bacterial gene for neomycin resistance or a mutant dihydrofolate reductase gene that confers resistance to methotrexate and have used these vectors to infect and confer drug resistance to human haematopoietic progenitor cells in vitro. Transfer could be demonstrated in the absence of helper virus by using an amphotropic retrovirus packaging cell line, PA12 (ref. 9). These studies are an important step towards the eventual application of retrovirus-mediated gene transfer to human gene therapy and for molecular approaches to the study of human haematopoiesis.     

大学生网络成瘾现象的调查研究

对2209名在校大学生进行调查,发现有近1/3的大学生存在不同程度的用网问题,而网络的特点、大学生自 我同一性发展以及他们的学习、交友与父母的关系等方面是导致网络成瘾的主要原因,为了有效防范网络成瘾,需要加 强教育与管理、咨询与治疗。     

microRNA-16 expression in HeLa cells is upregulated in cell-cycle and drug dependent manner

microRNAs are single-stranded, non-coding RNAs that regulate gene expression. The microRNA-16 family has been reported to be involved in cell-cycle regulation, which could also downregulate expression of multiple pro-proliferation genes. The present results demonstrated that miR-16 expression in HeLa cells increased when the cells were arrested during S-phase under methyl methanesulfate (MMS) treatment. This further resulted in downregulation of a target protein CDC25A, whereas miR-16 expression did not increase when HeLa cells were arrested during the MMS-treated G₀/G₁ or G₂/M phase. Furthermore, when HeLa cells were arrested during S-phase with hydroxyurea treatment, miR-16 expression did not increase. These results suggest that expression levels of microRNAs in mammalian cells are delicately regulated under variable cellular conditions.     

Systematic identification of genomic markers of drug sensitivity in cancer cells

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.