Decreased axonal density and altered expression profiles of axonal guidance genes underlying lead (Pb) neurodevelopmental toxicity at early embryonic stages in the zebrafish.
Decreased axonal density and altered expression profiles of axonal guidance genes underlying lead (Pb) neurodevelopmental toxicity at early embryonic stages in the zebrafish.
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DOI：
10.1016/j.ntt.2011.07.010
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发表时间：
2011-11
影响因子：
2.9
通讯作者：
Freeman, Jennifer L.
中科院分区：
文献类型：
--
作者：
Zhang, Jun;Peterson, Samuel M.;Weber, Gregory J.;Zhu, Xinqiang;Zheng, Wei;Freeman, Jennifer L.
先前的研究报告称，环境铅（Pb）暴露会导致儿童神经系统改变，导致智商下降、注意力缺陷多动障碍以及阅读和学习能力下降。然而，神经发育形态的具体改变以及这些改变的潜在遗传机制尚未得到彻底明确。为了研究神经形态的改变并检验发育性铅神经毒性部分通过神经元生长和轴突运输功能的改变介导的假设，通过抗乙酰化α-微管蛋白染色在受精后36小时（hpf）的几个发育时间点观察胚胎斑马鱼大脑中特定轴突束的变化。此外，还通过实时定量 PCR (qPCR) 研究了轴突发生相关基因子集的作用，包括 shha、epha4b、netrin1b、netrin2 和 noi。 Pb 处理导致中脑和前脑特定轴突束在 18、20 和 24 hpf 时的轴突密度降低。这些观察结果分别对应于观察到的 shha 和 epha4b 在 14 和 16 hpf 时的下调。铅暴露个体在后期（30 和 36 hpf）的轴突密度与对照组没有显着差异。 netrin2 在这两个发育阶段的过度表达表明该基因在调节 Pb 神经毒性特异性轴突密度方面具有新作用。尽管在两个后期发育阶段没有观察到轴突密度的显着差异，但需要进一步研究以确定早期阶段观察到的形态变化是否会产生持久的功能影响。
Previous studies have reported that environmental lead (Pb) exposure can result in neurological alterations in children leading to reduced IQ, attention deficit hyperactivity disorder, and diminished reading and learning abilities. However, the specific alterations in neurodevelopmental morphology and the underlying genetic mechanisms of these alterations have not yet been thoroughly defined. To investigate alterations in neurologic morphology and test the hypothesis that developmental Pb neurotoxicity is partially mediated through alterations in neuronal growth and transport function of axons, the changes of specific axon tracts in the embryonic zebrafish brain were observed with anti-acetylated α-tubulin staining at several developmental time points through 36 hours post fertilization (hpf). In addition, the role of a subset of axonogenesis-related genes including shha, epha4b, netrin1b, netrin2, and noi were investigated with real-time quantitative PCR (qPCR). Pb treatment resulted in decreased axonal density at 18, 20, and 24 hpf for specific axon tracts in the midbrain and forebrain. These observations corresponded to an observed down-regulation of shha and epha4b at 14 and 16 hpf, respectively. The axonal density in Pb exposed individuals at later stages (30 and 36 hpf) was not significantly different from controls. An overexpression of netrin2 at these two developmental stages suggests a novel role for this gene in regulating axonal density specific to Pb neurotoxicity. Although no significant differences in axonal density was observed in the two later developmental stages, further studies are needed to determine if the morphologic alterations observed at the earlier stages will have lasting functional impacts.
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影响因子：
2.9
作者：
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