Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric dis-orders. Developmental lead exposure can cause neurological disorders similar to hyperactivity dis-order, dyslexia and s...Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric dis-orders. Developmental lead exposure can cause neurological disorders similar to hyperactivity dis-order, dyslexia and schizophrenia. In the present study, we examined the impact of developmental lead exposure, administered in vitro and in vivo, on hippocampal Disrupted-In- Schizophrenia 1 expression. Our results show that in cultured hippocampal neurons, in vitro exposure to 0.1-10 μM lead, inhibited neurite growth and increased Disrupted-In-Schizophrenia 1 mRNA and protein ex-pression dose-dependently. In addition, blood lead levels in mice were increased with increasing mouse maternal lead (0.01-1 mM) exposure. Hippocampal neurons from these mice showed a concomitant increase in Disrupted-In-Schizophrenia 1 mRNA and protein expression. Overall our findings suggest that in vivo and in vitro lead exposure increases Disrupted-In-Schizophrenia 1 ex-pression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.展开更多
目的基因的表观修饰与阿尔茨海默病(AD)的发生密切相关,精神分裂症断裂基因1(disrupted in schizophrenia1,DISC1)是AD的候选基因。然而DISC1启动子甲基化与AD发生的关系尚不清楚。方法采用亚硫酸氢盐转化后焦磷酸测序分析的方法检测中...目的基因的表观修饰与阿尔茨海默病(AD)的发生密切相关,精神分裂症断裂基因1(disrupted in schizophrenia1,DISC1)是AD的候选基因。然而DISC1启动子甲基化与AD发生的关系尚不清楚。方法采用亚硫酸氢盐转化后焦磷酸测序分析的方法检测中国汉族51例AD患者和63例健康对照者血液样本中DISC1的甲基化水平。采用标准方法检测血样中各生化指标。结果AD组DISC1的甲基化水平显著高于健康对照组(P=0.002)。载脂蛋白A(apolipoprotein A,ApoA)、血清脂蛋白(lipoprotein A,Lp(a))和DISC1 CpG3甲基化之间发现了显著的关联。其中,女性AD患者中DISC1甲基化与血浆ApoA水平呈正相关(P=0.010,P=0.003)。男性AD患者中DISC1甲基化与血浆Lp(a)水平呈正相关(P<0.0001)。DISC1启动子甲基化的曲线下面积(area under curve,AUC)为0.726(95%CI:0.626~0.827),灵敏度和特异度分别为0.569和0.869。结论外周血DISC1启动子高甲基化是AD发生的高风险因素,其可能是AD诊断的潜在生物标志物。展开更多
基金supported by the National Nature Science Foundation of China, No. 39970651a Foundation from China Medical University
文摘Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric dis-orders. Developmental lead exposure can cause neurological disorders similar to hyperactivity dis-order, dyslexia and schizophrenia. In the present study, we examined the impact of developmental lead exposure, administered in vitro and in vivo, on hippocampal Disrupted-In- Schizophrenia 1 expression. Our results show that in cultured hippocampal neurons, in vitro exposure to 0.1-10 μM lead, inhibited neurite growth and increased Disrupted-In-Schizophrenia 1 mRNA and protein ex-pression dose-dependently. In addition, blood lead levels in mice were increased with increasing mouse maternal lead (0.01-1 mM) exposure. Hippocampal neurons from these mice showed a concomitant increase in Disrupted-In-Schizophrenia 1 mRNA and protein expression. Overall our findings suggest that in vivo and in vitro lead exposure increases Disrupted-In-Schizophrenia 1 ex-pression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.
基金support from the National Key Basic Research and Devdopment Program(973),Grant No.2011CB707805the Natural Science Foundation of China,Grant Nos.81000582 and 60831004+1 种基金the National High Technology Research and Development Program of China(863 Program), Grant No.2009AA02Z302The Beijing Nova Program,Grant No.2010B061
文摘目的基因的表观修饰与阿尔茨海默病(AD)的发生密切相关,精神分裂症断裂基因1(disrupted in schizophrenia1,DISC1)是AD的候选基因。然而DISC1启动子甲基化与AD发生的关系尚不清楚。方法采用亚硫酸氢盐转化后焦磷酸测序分析的方法检测中国汉族51例AD患者和63例健康对照者血液样本中DISC1的甲基化水平。采用标准方法检测血样中各生化指标。结果AD组DISC1的甲基化水平显著高于健康对照组(P=0.002)。载脂蛋白A(apolipoprotein A,ApoA)、血清脂蛋白(lipoprotein A,Lp(a))和DISC1 CpG3甲基化之间发现了显著的关联。其中,女性AD患者中DISC1甲基化与血浆ApoA水平呈正相关(P=0.010,P=0.003)。男性AD患者中DISC1甲基化与血浆Lp(a)水平呈正相关(P<0.0001)。DISC1启动子甲基化的曲线下面积(area under curve,AUC)为0.726(95%CI:0.626~0.827),灵敏度和特异度分别为0.569和0.869。结论外周血DISC1启动子高甲基化是AD发生的高风险因素,其可能是AD诊断的潜在生物标志物。
