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
目的调查多巴胺D2受体(DRD2)基因rs1800497多态性与慢性精神分裂症发病和认知功能的关系。方法招募567例慢性精神分裂症患者和421例健康受试者,认知功能采用重复性成套神经心理状态测验量表(RBANS)评估,DRD2基因rs1800497多态性采用Taq ...目的调查多巴胺D2受体(DRD2)基因rs1800497多态性与慢性精神分裂症发病和认知功能的关系。方法招募567例慢性精神分裂症患者和421例健康受试者,认知功能采用重复性成套神经心理状态测验量表(RBANS)评估,DRD2基因rs1800497多态性采用Taq Man SNP方法进行基因分型为:C/C、C/T、T/T。收集一般人口学和临床数据。结果慢性精神分裂症组和健康对照组DRD2基因rs1800497位点的等位基因频率的分布没有显著性差异(χ~2=0.05,df=1,P=0.83),但基因型频率的分布出现显著性差异(χ~2=7.00,df=2,P=0.03)。精神分裂症患者依据rs1800497位点基因型分组分析:组间延迟记忆分值出现显著差异(F=3.91,P=0.02)。结论DRD2基因rs1800497位点可能参与了精神分裂症的发病,并进一步可能影响精神分裂症的认知功能。展开更多
试验旨在研究多巴胺受体D2(dopamine receptor D2,DRD2)基因多态性及其与欣华鸡蛋用性状的相关性,寻找可用于欣华鸡蛋用性状选育的分子遗传标记。应用Primer Premier 5.0软件设计4对引物,利用PCR-RFLP技术对欣华E系鸡群的473个个体进行...试验旨在研究多巴胺受体D2(dopamine receptor D2,DRD2)基因多态性及其与欣华鸡蛋用性状的相关性,寻找可用于欣华鸡蛋用性状选育的分子遗传标记。应用Primer Premier 5.0软件设计4对引物,利用PCR-RFLP技术对欣华E系鸡群的473个个体进行基因型鉴定,使用SPSS 19.0软件将欣华鸡的蛋用性状与DRD2基因多态性进行关联分析。群体多态性分析结果表明,存在4个SNPs位点:A-16105G(SNP1)、G-12510T(SNP2)、G+3360A(SNP3)和T+5042C(SNP4),其中SNP1和SNP2位点符合哈代-温伯格平衡(P>0.05),且杂合度较低,但SNP3和SNP4位点显著偏离哈代-温伯格平衡(P<0.05)。关联分析表明,DRD2基因4个SNPs位点与欣华E系鸡群体蛋用性状存在关联,其中与产蛋性状关联结果:SNP1与开产日龄显著关联(P<0.05),SNP2与33周龄产蛋数、300日龄产蛋总数极显著关联(P<0.01),SNP3与开产体重(P<0.05)、300日龄产蛋总数(P<0.01)、平均连产(P<0.01)和最长连产(P<0.05)关联,SNP4与开产日龄极显著关联(P<0.01);与蛋品质关联结果:SNP1与蛋形指数(P<0.01)、蛋黄颜色(P<0.01)和哈氏单位(P<0.05)关联,SNP2与蛋黄重显著关联(P<0.05),SNP3与蛋壳强度极显著关联(P<0.01),SNP4与蛋黄重、蛋清重和哈氏单位显著关联(P<0.05)。单倍型分析发现,DRD2基因4个SNPs位点的不同单倍型组合与欣华鸡的最长连产长度呈极显著相关(P<0.01),与哈氏单位呈显著相关(P<0.05)。组织表达谱分析发现,DRD2基因主要在欣华E系鸡垂体中表达,在58周龄鸡胸肌中有较高表达,在36周龄鸡脑中有少量表达。结果表明,DRD2基因可作为候选基因辅助用于欣华E系鸡群体蛋用性状的遗传改良。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.
文摘目的调查多巴胺D2受体(DRD2)基因rs1800497多态性与慢性精神分裂症发病和认知功能的关系。方法招募567例慢性精神分裂症患者和421例健康受试者,认知功能采用重复性成套神经心理状态测验量表(RBANS)评估,DRD2基因rs1800497多态性采用Taq Man SNP方法进行基因分型为:C/C、C/T、T/T。收集一般人口学和临床数据。结果慢性精神分裂症组和健康对照组DRD2基因rs1800497位点的等位基因频率的分布没有显著性差异(χ~2=0.05,df=1,P=0.83),但基因型频率的分布出现显著性差异(χ~2=7.00,df=2,P=0.03)。精神分裂症患者依据rs1800497位点基因型分组分析:组间延迟记忆分值出现显著差异(F=3.91,P=0.02)。结论DRD2基因rs1800497位点可能参与了精神分裂症的发病,并进一步可能影响精神分裂症的认知功能。
