Exposure to fine particulate matter (PM2.5) is implicated in neurodevelopmental disorders including cognitive decline, attention-deficit/hyperactivity disorder, and autism spectrum disorder. However, the specific molecular mechanisms by which PM2.5 impacts neurodevelopment are poorly understood. Accordingly, in the present study, the role of protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling in PM2.5-induced neurodevelopmental damage was investigated using primary cultured hippocampal neurons.

When hippocampal neurons cultured for 3 days in vitro (DIV3) were exposed to PM2.5 for 24 h and 96 h, neuronal viability decreased by 18.8% and 32.7% respectively, percentage of TUNEL-positive neurons increased by 78.5% and 64.0% separately, caspase-9 expression increased, lower postsynaptic density and shorter active zones were observed by transmission electron microscopy, expression of synapse-related proteins including postsynaptic density-95 (PSD95), growth associated protein-43 (GAP43), and synaptophysin (SYP) were decreased, and the phosphorylation levels of PKA, CREB, and BDNF expression also decreased. However, the PM2.5-induced neuronal damage could be ameliorated or aggravated to varying degrees by up- or down-regulation of the PKA/CREB/BDNF signaling pathway, respectively.

Our results indicate that PM2.5 exposure exerts neurodevelopmental toxicity as indicated by lower viability, apoptosis, and synaptic damage in primary cultured hippocampal neurons, and that the PKA/CREB/BDNF pathways could play a vital role in PM2.5-mediated neurodevelopmental toxicity.

细颗粒物（PM2.5）的暴露与神经发育障碍有关，包括认知能力下降，注意力缺陷/多动障碍和自闭症谱系障碍。然而，人们对PM2.5影响神经发育的特定分子机制了解甚少。因此，在本研究中，使用原代培养的海马神经元研究了蛋白激酶A（PKA）/ cAMP反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）信号在PM2.5诱导的神经发育损伤中的作用。 。

将体外培养3天的海马神经元（DIV3）暴露于PM2.5 24小时和96小时，神经元活力分别降低了18.8％和32.7％，TUNEL阳性神经元的百分比分别增加了78.5％和64.0％ ，透射电镜观察到caspase-9表达增加，突触后密度降低和活性区缩短，包括突触后密度95（PSD95），生长相关蛋白43（GAP43）和突触素（SYP）在内的突触相关蛋白的表达降低，并且PKA，CREB和BDNF表达的磷酸化水平也降低。但是，分别通过上调或下调PKA / CREB ​​/ BDNF信号通路可以不同程度地改善或加剧PM2.5诱导的神经元损伤。

我们的结果表明，PM2.5暴露具有神经发育毒性，如原代培养的海马神经元的活力降低，凋亡和突触损伤所表明的那样，并且PKA / CREB ​​/ BDNF途径可能在PM2.5介导的神经发育毒性中起重要作用。