With the help of particulate matter, benzo(a)pyrene (BaP) has become a widely distributed environmental contaminant. In addition to the well-known carcinogenicity, a growing number of studies have focused on the neurotoxicity of BaP, especially on adverse neurobehavioral effects. However, the molecular modulating mechanisms remain unclear. In this paper, we confirmed that BaP exposure produced a neuronal insult via its metabolite benzo(a)pyrene diol epoxide (BPDE) on the primary cultured cortical neuron in vitro and mice in vivo models, and the effects were largely achieved by activating cyclooxygenases-2 (COX-2) enhancement. Also, the action of BaP on elevating COX-2 was initiated by BPDE firmly binding to the active pockets of COX-2, then followed by the production of prostaglandin E₂ (PGE₂) and upregulation of its EP2 and EP4 receptors, finally stimulating the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway. Our results reveal a mechanistic association underlying BaP exposure and increased risk for neurological dysfunction and clarify the ways to prevent and treat brain injuries in polluted environments.

中文翻译：

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环氧合酶2在苯并（a）re诱导的皮质神经元神经毒性中的作用。

借助于颗粒物，苯并（a）re（BaP）已成为分布广泛的环境污染物。除了众所周知的致癌性外，越来越多的研究集中在BaP的神经毒性上，尤其是在不良的神经行为影响上。但是，分子调节机制仍不清楚。在本文中，我们证实了BaP暴露会通过其代谢产物苯并（a）二醇环氧化物（BPDE）在体外和小鼠体内培养的皮层神经元上产生神经元损伤。通过激活环加氧酶2（COX-2）增强，可在很大程度上获得效果。而且，BaP升高COX-2的作用是通过BPDE牢固结合到COX-2的活性口袋而引发的，然后产生前列腺素E ₂（PGE ₂）并上调其EP2和EP4受体，从而最终刺激环状单磷酸腺苷/蛋白激酶A（cAMP / PKA）信号通路。我们的研究结果揭示了BaP暴露与神经功能障碍风险增加之间的机械关联，并阐明了在污染环境中预防和治疗脑损伤的方法。