Long-term exposure to fine particulate matter (PM_2.5) has been reported to be closely associated with the neuroinflammation and synaptic dysfunction, but the mechanisms underlying the process remain unclear. Cyclooxygenase-2 (COX-2) is a key player in neuroinflammation, and has been also implicated in the glutamatergic excitotoxicity and synaptic plasticity. Thus, we hypothesized that COX-2 was involved in PM_2.5-promoted neuroinflammation and synaptic dysfunction. Our results revealed that PM_2.5 elevated COX-2 expression in primary cultured hippocampal neurons and increased the amplitude of field excitatory postsynaptic potentials (fEPSPs) in hippocampal brain slices. And the administration of NS398 (a COX-2 inhibitor) prevented the increased fEPSPs. PM_2.5 also induced intracellular reactive oxygen species (ROS) generation accompanied with glutathione (GSH) depletion and the loss of mitochondrial membrane potential (MMP), and the ROS inhibitor, N-acetyl-L-cystein (NAC) suppressed the COX-2 overexpression and the increased fEPSPs. Furthermore, the nuclear factor kappa B (NF-κB) was involved in ROS-induced COX-2 and fEPSP in response to PM_2.5 exposure. These findings indicated that PM_2.5 activated COX-2 expression and enhanced the synaptic transmission through ROS-NF-κB pathway, and provided possible biomarkers and specific interventions for PM_2.5-induced neurological damage.

中文翻译：

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PM _2.5暴露可通过ROS-NF-κB途径刺激COX-2介导的兴奋性突触传递。

据报道，长期接触细颗粒物（PM _2.5）与神经炎症和突触功能障碍密切相关，但尚不清楚该过程的潜在机制。环氧合酶2（COX-2）是神经炎症的关键因素，也与谷氨酸能兴奋性毒性和突触可塑性有关。因此，我们假设COX-2参与了PM _2.5促进的神经炎症和突触功能障碍。我们的研究结果表明，PM _2.5在原代培养的海马神经元中升高了COX-2的表达，并增加了海马脑片中场兴奋性突触后突触电位（fEPSPs）的幅度。NS398（一种COX-2抑制剂）的给药可防止fEPSP升高。下午_2.5还诱导了细胞内活性氧（ROS）的产生并伴随着谷胱甘肽（GSH）的消耗和线粒体膜电位（MMP）的损失，并且ROS抑制剂N-乙酰基-L-半胱氨酸（NAC）抑制了COX-2的过表达和增加的fEPSP。此外，核因子κB（NF-κB）参与了ROS诱导的COX-2和fEPSP，以响应PM _2.5暴露。这些发现表明，PM _2.5激活了COX-2的表达并增强了通过ROS-NF-κB途径的突触传递，并为PM _2.5诱导的神经系统损伤提供了可能的生物标志物和特异性干预措施。