Abstract：
1-Nitropyrene (1-NP) is a neurodevelopmental toxicant. This study was to evaluate the impact of exposure to 1-NP after weaning on anxiety-like behavior. Five-week-old mice were administered with 1-NP (0.1 or 1 mg/kg) daily for 4 weeks. Anxiety-like behaviour was measured using elevated-plus maze (EPM) and open field test (OFT). In EPM test, time spending in open arm and times entering open arm were reduced in 1-NP-treated mice. In OFT test, time spent in the center region and times entering the center region were diminished in 1-NP-treated mice. Prefrontal dendritic length and number of dendrite branches were decreased in 1-NP-treated mice. Prefrontal PSD95, an excitatory postsynaptic membrane protein, and gephyrin, an inhibitory postsynaptic membrane protein, were downregulated in 1-NP-treated mice. Further analysis showed that peripheral steroid hormones, including serum testosterone (T) and estradiol (E2), testicular T, and ovarian E2, were decreased in 1-NP-treated mice. Interestingly, T and E2 were diminished in 1-NP-treated prefrontal cortex. Prefrontal T and E2 synthases were diminished in 1-NP-treated mice. Mechanistically, GCN2-eIF2α, a critical pathway that regulates ribosomal protein translation, was activated in 1-NP-treated prefrontal cortex. These results indicate that exposure to 1-NP after weaning induces anxiety-like behaviour partially by inhibiting steroid hormone synthesis in prefrontal cortex.
摘要：
1-硝基芘（1-NP）是一种神经发育毒物。本研究旨在评估断奶后暴露于1-NP对焦虑样行为的影响。5周龄的小鼠每天施用1-NP(0.1或1mg/kg),持续4周。使用高架迷宫（EPM）和开放场测试（OFT）测量焦虑样行为。在EPM测试中，在1-NP处理的小鼠中,开放臂的时间和进入开放臂的时间减少.在OFT测试中，在1-NP处理的小鼠中,在中心区域花费的时间和进入中心区域的时间减少.1-NP处理的小鼠前额叶树突长度和树突分支数量减少。前额叶PSD95，一种兴奋性突触后膜蛋白，和卟啉,一种抑制性突触后膜蛋白，在1-NP处理的小鼠中下调。进一步分析显示外周类固醇激素,包括血清睾酮（T）和雌二醇（E2），睾丸T,和卵巢E2在1-NP处理的小鼠中降低。有趣的是,在1-NP处理的前额叶皮层中T和E2减少。在1-NP处理的小鼠中前额叶T和E2合酶减少。机械上,GCN2-eIF2α,调节核糖体蛋白翻译的关键途径，在1-NP处理的前额叶皮层中被激活。这些结果表明，断奶后暴露于1-NP会部分通过抑制前额叶皮质类固醇激素的合成而导致焦虑样行为。
