Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mic...Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.展开更多
目的探讨DRD2和DRD3基因多态性与利培酮治疗精神分裂症临床疗效间的关系.方法共106例中国西南地区汉族精神分裂症患者接受单一利培酮治疗12周,应用阴性和阳性症状量表(Positive and Negative Syndrome Scale,PANSS)、个人和社会功能量表...目的探讨DRD2和DRD3基因多态性与利培酮治疗精神分裂症临床疗效间的关系.方法共106例中国西南地区汉族精神分裂症患者接受单一利培酮治疗12周,应用阴性和阳性症状量表(Positive and Negative Syndrome Scale,PANSS)、个人和社会功能量表(Personal and Social Performance Scale,PSP)、瑞文标准推理测验、韦氏智能测验数字识记法、数字划消测验分别对患者进行基线和12周末的测评,同时收集同一地区汉族健康对照178例;采用Taq Man等位基因分型方法对DRD2和DRD3基因的3个多态性位点(rs1800496,rs6276,rs6280)进行基因分型,SHEsis在线软件来检测Hardy-Weinberg平衡、基因型和等位基因频率分析.采用SPSS17.0统计软件包进行统计分析.结果 (1)rs1800496对照组和实验组均为单一基因型AG,未见纯合子,不是基因多态性位点;(2)精神分裂症组与对照组在2个多态性位点的基因型分布和等位基因频率上均无统计学差异(P>0.05);(3)治疗前,DRD2基因rs6276三种基因型患者在基线PANSS阴性症状得分上的差异具有统计学意义(P=0.007).治疗后,DRD2基因rs6276三种基因型在治疗前后PANSS阴性症状得分差值(P=0.002)以及PSP总分差值上的差异具有统计学意义(P=0.024).结论利培酮治疗精神分裂症疗效显著,对部分认知功能有改善作用,DRD2基因的rs6276多态性可能与利培酮治疗精神分裂症阴性症状的改善有关系,DRD3基因的rs6280多态性可能与利培酮治疗精神分裂症的疗效无关.展开更多
文摘Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.
文摘目的探讨DRD2和DRD3基因多态性与利培酮治疗精神分裂症临床疗效间的关系.方法共106例中国西南地区汉族精神分裂症患者接受单一利培酮治疗12周,应用阴性和阳性症状量表(Positive and Negative Syndrome Scale,PANSS)、个人和社会功能量表(Personal and Social Performance Scale,PSP)、瑞文标准推理测验、韦氏智能测验数字识记法、数字划消测验分别对患者进行基线和12周末的测评,同时收集同一地区汉族健康对照178例;采用Taq Man等位基因分型方法对DRD2和DRD3基因的3个多态性位点(rs1800496,rs6276,rs6280)进行基因分型,SHEsis在线软件来检测Hardy-Weinberg平衡、基因型和等位基因频率分析.采用SPSS17.0统计软件包进行统计分析.结果 (1)rs1800496对照组和实验组均为单一基因型AG,未见纯合子,不是基因多态性位点;(2)精神分裂症组与对照组在2个多态性位点的基因型分布和等位基因频率上均无统计学差异(P>0.05);(3)治疗前,DRD2基因rs6276三种基因型患者在基线PANSS阴性症状得分上的差异具有统计学意义(P=0.007).治疗后,DRD2基因rs6276三种基因型在治疗前后PANSS阴性症状得分差值(P=0.002)以及PSP总分差值上的差异具有统计学意义(P=0.024).结论利培酮治疗精神分裂症疗效显著,对部分认知功能有改善作用,DRD2基因的rs6276多态性可能与利培酮治疗精神分裂症阴性症状的改善有关系,DRD3基因的rs6280多态性可能与利培酮治疗精神分裂症的疗效无关.
