You Yuanyuan, Sun Liguang, Peng Bo, Li Yan, Ben Songbin, Gao Shuang
Department of Biochemical and Molecular Biology, China Medical University, Shenyang 110001, Liaoning Province, China.
Outpatient Department of China Medical University, Shenyang 110001, Liaoning Province, China.
Neural Regen Res. 2012 Sep 5;7(25):1939-45. doi: 10.3969/j.issn.1673-5374.2012.25.003.
Disrupted-In-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric disorders. Developmental lead exposure can cause neurological disorders similar to hyperactivity disorder, 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 expression 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 expression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.
精神分裂症相关基因1是精神分裂症和其他精神障碍的一个易感基因。发育过程中铅暴露可导致类似于多动症、阅读障碍和精神分裂症的神经障碍。在本研究中，我们检测了体外和体内发育过程中铅暴露对海马体中精神分裂症相关基因1表达的影响。我们的结果表明，在培养的海马神经元中，体外暴露于0.1 - 10µM铅会抑制神经突生长，并剂量依赖性地增加精神分裂症相关基因1的mRNA和蛋白质表达。此外，随着小鼠母体铅暴露量（0.01 - 1 mM）的增加，小鼠血液中的铅水平升高。来自这些小鼠的海马神经元显示出精神分裂症相关基因1的mRNA和蛋白质表达随之增加。总体而言，我们的研究结果表明，体内和体外铅暴露都会剂量依赖性地增加海马神经元中精神分裂症相关基因1的表达，因此可能会影响新生神经元中的突触形成。
