Studies from postmortem and animal models have revealed altered synapse morphology and function in the brain of posttraumatic stress disorder (PTSD). And the effects of PTSD on dendrites and spines have been reported, however, the effection on axon include microtubule (MT) and synaptic vesicles of presynaptic elements remains unknown. Hippocampus is involved in abnormal memory in PTSD. In the present study, we used the single prolonged stress (SPS) model to mimic PTSD. Quantitative real-time polymerase chain reaction (RT-qPCR) and high-throughput sequencing (GSE153081) were utilized to analyze differentially expressed genes (DEGs) in the hippocampus of control and SPS rats. Immunofluorescence and western blotting were performed to examine change in axon-related proteins. Synaptic function was evaluated by measuring miniature excitatory postsynaptic currents (mEPSCs). RNA-sequencing analysis revealed 230 significantly DEGs between the control and SPS groups. Gene Ontology analysis revealed upregulation in axonemal assembly, MT formation, or movement, but downregulation in axon initial segment and synaptic vesicles fusion in the hippocampus of SPS rats. Increased expression in tau, β-tubulin MAP1B, KIF9, CCDC40, DNAH12 and decreased expression in p-tau, stathmin suggested SPS induced axon extension. Increased protein expression in VAMP, STX1A, Munc18-1 and decreased expression in synaptotagmin-1 suggested SPS induced more SNARE complex formation but decreased ability in synaptic vesicle fusion to presynaptic active zone membrane in the hippocampus of SPS rats. Further, low mEPSC frequency in SPS rats indicated dysfunction in presynaptic membrane. These results suggest that axon extension and synaptic vesicles fusion abnormality are involved in dysfunction of PTSD.

尸检和动物模型的研究揭示了创伤后应激障碍 (PTSD) 大脑中突触形态和功能的改变。并且已经报道了PTSD对树突和棘的影响，但是，对轴突的影响包括微管（MT）和突触前元件的突触小泡仍然未知。海马参与了创伤后应激障碍的异常记忆。在本研究中，我们使用单一长期压力 (SPS) 模型来模拟 PTSD。利用定量实时聚合酶链反应 (RT-qPCR) 和高通量测序 (GSE153081) 分析对照和 SPS 大鼠海马中的差异表达基因 (DEG)。进行免疫荧光和蛋白质印迹以检查轴突相关蛋白的变化。通过测量微型兴奋性突触后电流 (mEPSC) 来评估突触功能。RNA 测序分析显示对照组和 SPS 组之间有 230 个显着的 DEG。基因本体分析显示轴突组装、MT 形成或运动上调，但轴突初始节段和 SPS 大鼠海马中突触小泡融合的下调。tau、β-微管蛋白 MAP1B、KIF9、CCDC40、DNAH12 中的表达增加而 p-tau 中的表达降低，stathmin 表明 SPS 诱导轴突延伸。VAMP、STX1A、Munc18-1 中的蛋白表达增加和突触结合蛋白-1 中的表达降低表明 SPS 诱导了更多的 SNARE 复合物形成，但降低了 SPS 大鼠海马突触小泡与突触前活性区膜融合的能力。进一步，SPS 大鼠的低 mEPSC 频率表明突触前膜功能障碍。这些结果表明轴突延伸和突触小泡融合异常与PTSD功能障碍有关。