以0、3.7×103、3.7×104、3.7×105及3.7×106Bq/mL的氚水(HTO)照射原代培养的神经细胞,照后24小时用Leica AF 6000活细胞工作站测细胞迁移距离,Fluo-3-AM荧光探针负载和流式细胞仪测定细胞内游离钙离子浓度,Western b...以0、3.7×103、3.7×104、3.7×105及3.7×106Bq/mL的氚水(HTO)照射原代培养的神经细胞,照后24小时用Leica AF 6000活细胞工作站测细胞迁移距离,Fluo-3-AM荧光探针负载和流式细胞仪测定细胞内游离钙离子浓度,Western blot法分析细胞内β-tubulin和NCAM蛋白变化,以探讨氚β辐射影响神经细胞迁移的机制。结果发现,随着氚水浓度增大,氚照射剂量的增加,神经细胞迁移距离逐渐减小,细胞内游离钙离子逐渐增多,β-tubulin和NCAM表达逐渐减弱。提示氚β辐射可使神经细胞迁移相关调控因子产生变化,影响其迁移。展开更多
人类大脑皮层发育过程中,大量神经细胞从靠近脑室的增殖区产生并向软脑膜方向迁移,最终形成与人类许多高级功能相关的6层大脑新皮质结构,Reelin-Dab1信号通路在神经细胞迁移中起到了关键的作用。Reelin结合于迁移细胞膜上的极低密度脂...人类大脑皮层发育过程中,大量神经细胞从靠近脑室的增殖区产生并向软脑膜方向迁移,最终形成与人类许多高级功能相关的6层大脑新皮质结构,Reelin-Dab1信号通路在神经细胞迁移中起到了关键的作用。Reelin结合于迁移细胞膜上的极低密度脂蛋白受体(very lowlipoprotein recep-tor,VLDLR)和载脂蛋白E受体2(apolipoprotein E receptor2,ApoER2),磷酸化胞浆内的衔接蛋白disabled1(Dab1),继而与下游信号分子如细胞骨架蛋白等相互作用,指导皮层神经元的正确迁移和定位。本篇综述讨论了Reelin-Dab1信号通路在人类新皮质形成过程中的作用及近几年的研究新进展。展开更多
Ephrin ligands interact with Eph receptors to regulate a wide variety of biological and pathological processes. Recent studies have identified several downstream pathways that mediate the functions of these receptors....Ephrin ligands interact with Eph receptors to regulate a wide variety of biological and pathological processes. Recent studies have identified several downstream pathways that mediate the functions of these receptors. Activation of the receptors by ephrin binding results in the phosphorylation of the receptor tyrosine residues. These phospho- rylated residues serve as docking sites for many of the downstream signaling pathways. However, the relative contributions of different phosphotyrosine residues remain undefined. In the present study, we mutated each individual tyrosine residues in the cytoplasmic domain of EphA3 receptor and studied the effects using cell migration, process retraction, and growth cone collapse assays. Stimulation of the EphA3 receptor with ephrin-A5 inhibits 293A cell mi- gration, reduces NG108-15 cell neurite outgrowth, and induces growth cone collapse in hippocampal neurons. Muta- tion of either Y602 or Y779 alone partially decreases EphA3-induced responses. Full abrogation can only be achieved with mutations of both Y602 and Y779. These observations suggest a collaborative model of different downstream pathways.展开更多
Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in th...Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.展开更多
文摘以0、3.7×103、3.7×104、3.7×105及3.7×106Bq/mL的氚水(HTO)照射原代培养的神经细胞,照后24小时用Leica AF 6000活细胞工作站测细胞迁移距离,Fluo-3-AM荧光探针负载和流式细胞仪测定细胞内游离钙离子浓度,Western blot法分析细胞内β-tubulin和NCAM蛋白变化,以探讨氚β辐射影响神经细胞迁移的机制。结果发现,随着氚水浓度增大,氚照射剂量的增加,神经细胞迁移距离逐渐减小,细胞内游离钙离子逐渐增多,β-tubulin和NCAM表达逐渐减弱。提示氚β辐射可使神经细胞迁移相关调控因子产生变化,影响其迁移。
文摘人类大脑皮层发育过程中,大量神经细胞从靠近脑室的增殖区产生并向软脑膜方向迁移,最终形成与人类许多高级功能相关的6层大脑新皮质结构,Reelin-Dab1信号通路在神经细胞迁移中起到了关键的作用。Reelin结合于迁移细胞膜上的极低密度脂蛋白受体(very lowlipoprotein recep-tor,VLDLR)和载脂蛋白E受体2(apolipoprotein E receptor2,ApoER2),磷酸化胞浆内的衔接蛋白disabled1(Dab1),继而与下游信号分子如细胞骨架蛋白等相互作用,指导皮层神经元的正确迁移和定位。本篇综述讨论了Reelin-Dab1信号通路在人类新皮质形成过程中的作用及近几年的研究新进展。
文摘Ephrin ligands interact with Eph receptors to regulate a wide variety of biological and pathological processes. Recent studies have identified several downstream pathways that mediate the functions of these receptors. Activation of the receptors by ephrin binding results in the phosphorylation of the receptor tyrosine residues. These phospho- rylated residues serve as docking sites for many of the downstream signaling pathways. However, the relative contributions of different phosphotyrosine residues remain undefined. In the present study, we mutated each individual tyrosine residues in the cytoplasmic domain of EphA3 receptor and studied the effects using cell migration, process retraction, and growth cone collapse assays. Stimulation of the EphA3 receptor with ephrin-A5 inhibits 293A cell mi- gration, reduces NG108-15 cell neurite outgrowth, and induces growth cone collapse in hippocampal neurons. Muta- tion of either Y602 or Y779 alone partially decreases EphA3-induced responses. Full abrogation can only be achieved with mutations of both Y602 and Y779. These observations suggest a collaborative model of different downstream pathways.
基金supported by grants from the National Natural Sciences Foundation of China(No.31470264,No.81271820,No.30870789,and No.30300117)the Key Program of Natural Science Foundation of Hubei Province of China(No.2014CFA078)+1 种基金the Stanley Foundation from the Stanley Medical Research Institute(SMRI),USA(No.06R-1366),to Dr.Fan Zhuthe Scientific Innovation Team Project of Hubei Province of China(No.2015CFA009)
文摘Human endogenous retrovirus W env(HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis(MS). These diseases are accompanied by immunological reactions in the central nervous system(CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter – nitric oxide(NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase(hi NOS) and enhanced the promoter activity of hi NOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.
