Abstract
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.
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Data Availability
All data, models used during the study are available from the corresponding author by request.
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We thank Cloud-Seq Biotech Ltd. Co. (Shanghai, China) for the mRNA-Seq service and the subsequent bioinformatics analysis.
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This research was supported by a grant from the National Natural Science Foundation of China (No. 81571324) and the Science and Technology Plan Project of Liaoning Province, China (No. 2017225011) to FH.
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All authors contributed to the study conception and design; YG, XC, and BZ performed the experiments; YG, BZ, and XC analyzed the data and prepared figures; YG, YS, and FH wrote the paper; FH revised the manuscript for important intellectual content; All authors read and approved the final manuscript.
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Guan, Y., Chen, X., Zhao, B. et al. What Happened in the Hippocampal Axon in a Rat Model of Posttraumatic Stress Disorder. Cell Mol Neurobiol 42, 723–737 (2022). https://doi.org/10.1007/s10571-020-00960-w
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DOI: https://doi.org/10.1007/s10571-020-00960-w