What Happened in the Hippocampal Axon in a Rat Model of Posttraumatic Stress Disorder
Autor: | Fang Han, Beiying Zhao, Xinzhao Chen, Yuxiu Shi, Yadi Guan |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
education Hippocampus Synaptic vesicle Stress Disorders Post-Traumatic 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Animals Axon Chemistry STX1A Axon extension Cell Biology General Medicine Presynaptic active zone membrane Axon initial segment Axons Cell biology Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Excitatory postsynaptic potential 030217 neurology & neurosurgery |
Zdroj: | Cellular and molecular neurobiology. 42(3) |
ISSN: | 1573-6830 |
Popis: | 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. |
Databáze: | OpenAIRE |
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