The effects of lead on GABAergic interneurons in rodents
The effects of lead on GABAergic interneurons in rodents
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铅对啮齿动物 GABA 能中间神经元的影响
DOI：
10.1177/0748233717732902
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发表时间：
2017-11-01
影响因子：
1.9
通讯作者：
Jiang, Yongmei
中科院分区：
文献类型：
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作者：
Duan, Yifei;Peng, Leiwen;Jiang, Yongmei
铅是一种重金属，会影响人体的各种系统和器官，特别是神经系统。本研究分析了铅在体内和体外对神经元的影响。我们根据铅暴露的浓度将小鼠幼鼠分为三组：对照组、低剂量组和高剂量组。测定三组动物的行为变化(开场实验和尾部悬吊实验)、血铅水平(原子吸收分光光度法测量)、GABA能中间神经元数量(免疫组织化学测量)、基因表达(qRT-PCR测量)和DNA甲基化(焦磷酸测序测量)。铅暴露组小鼠的血铅水平显著高于对照组(P<；0.001)。与对照组相比，铅暴露可引起小鼠多动，体重减轻。染铅组大鼠大脑皮层小白蛋白和神经肽Y中间神经元数量显著减少，远端无同源盒(DLX)1、2、5和6基因表达水平降低。为了进一步阐明DLX基因下调的机制，我们选择了可以分化为不同亚型的GABA能中间神经元的GE6细胞株进行体外实验。我们发现高水平的铅在体外也抑制了DLX 1/2/5/6的表达，但在GE6细胞系中DNA甲基化水平没有改变。此外，体外染铅可显著降低细胞中的寡聚糖1和Ki67的表达，增加TUBB3的表达。本研究表明，铅暴露可改变行为，减少GABA能中间神经元的数量，并改变神经细胞中一些重要基因的表达。
Lead is a heavy metal that affects various systems and organs in the body, especially the nervous system. In this study, the in vivo and in vitro effects of lead on neurons were analyzed. We divided mouse pups into three groups based on the concentration of lead exposure: the control group, the low-dose group, and the high-dose group. Changes in behavior (measured by an open-field test and a tail suspension test), blood lead levels (measured by atomic absorption spectrophotometry), the number of GABAergic interneurons (measured by immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation (measured by pyrosequencing) were determined in the three groups. The lead-exposed pups showed significantly higher blood lead levels (p < 0.001). Lead exposure caused hyperactivity and reduced the body weight of the exposed mice compared with that of the controls. The lead-exposed groups showed significantly lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression levels of distal-less homeobox (Dlx) 1, 2, 5, and 6 genes in the cerebral cortex. To further clarify the mechanism of Dlx gene downregulation, we selected the GE6 cell line, which can differentiate into various subtypes of GABAergic interneurons, for in vitro experiments. We found that high levels of lead also inhibited the expression of Dlx 1/2/5/6 in vitro, but DNA methylation levels were not changed in the GE6 cell line. Furthermore, lead exposure significantly decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro. The present study revealed that lead exposure can alter behaviors, reduce the number of GABAergic interneurons, and change the expression of some important genes in neuronal cells.