Abstract

Synaptic plasticity plays an important role in learning and memory in the developing hippocampus. However, the precise molecular mechanism in lead exposure models remains to be studied. UCP2, an inner mitochondrial anion carrier, regulates synaptic plasticity through uncoupling neurons. And hnRNP K, an RNA binding protein, plays a role in modulating the expression of transcripts coding synaptic plasticity. We aim to investigate whether lead exposure affects UCP2 and hnRNP K expression levels. The Sprague-Dawley rats were exposed to different lead acetate concentrations (0 g/l, 0.5 g/l, 2.0 g/l) during gestational and lactational periods. PC12 cells were also exposed to different lead acetate concentrations (0 μM, 1 μM and 100 μM). We found that the expression levels of UCP2 and hnRNP K had significant declines in the lead exposure rat hippocampus and PC12 cells. Furthermore, the up-regulation of hnRNP K expression level could reverse the expression level of UCP2 in lead exposure models. In conclusion, these results suggest that lead exposure can reduce the expression level of UCP2 which is mediated by decreasing the expression level of hnRNP K.

摘要

突触可塑性在发育中的海马体的学习和记忆中起着重要作用。然而，铅暴露模型中的精确分子机制仍有待研究。UCP2 是一种内部线粒体阴离子载体，通过解偶联神经元调节突触可塑性。而 hnRNP K，一种 RNA 结合蛋白，在调节编码突触可塑性的转录本的表达中发挥作用。我们旨在调查铅暴露是否影响 UCP2 和 hnRNP K 表达水平。Sprague-Dawley 大鼠在妊娠期和哺乳期暴露于不同浓度的醋酸铅（0 g/l、0.5 g/l、2.0 g/l）。PC12 细胞也暴露于不同浓度的醋酸铅（0 μM、1 μM 和 100 μM）。我们发现铅暴露的大鼠海马和PC12细胞中UCP2和hnRNP K的表达水平显着下降。此外，hnRNP K 表达水平的上调可以逆转铅暴露模型中 UCP2 的表达水平。总之，这些结果表明铅暴露可以降低 UCP2 的表达水平，这是通过降低 hnRNP K 的表达水平介导的。