The Role of Cyclooxygenases-2 in Benzo(a)pyrene-Induced Neurotoxicity of Cortical Neurons

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.