The Pathological Changes In Important Brain Areas And The Significance About The Variation Of Zinc In PTSD Rats

Post-traumatic stress disorder?PTSD?is a mental disorder which will exist for a long time after a great stress events appeared.Imaging evidences had shown that the volume of hippocampus in people with PTSD is smaller than that of normal person,which suggests there may exists some pathological damages,but what the pathological damages like and how does that happens,it is not very clear yet,because there were no pathology evidences directly with PTSD patients in the clinic.In addition,as an important signal molecule in the brain,it has not been reported if the Zn²⁺ is involved in the occurrence of PTSD.Therefore,study on the characteristics and mechanisms of PTSD are necessary through the animal experiments.After the PTSD rats model were established successfully,we observed the pathological changes in the cortex and each regions of hippocampus about PTSD rats.Further more,we had tested the concentration of Zn²⁺,neurotransmitters and receptors in the hippocampus,finally,we discussed the potential roles and mechanisms of Zn²⁺ in the development of PTSD.Methods:?1?The establishment of the PTSD rat model.We established the model by complex stress.?2?The behavioral tests.Compared with the normal rats,we use the open field test,the elevated plus maze and Morris water maze to detect the behavior changes of rats in normal group and model group,with a series of index,we can judge if the rats in model group have the positive symptoms of PTSD.?3?The pathological study.Compared with the normal rats,HE staining and Nissl staining were performed to observe the pathological changes in cerebral cortex and areas of CA1,CA2,CA3,dentate gyrus in hippocampus of the model rats.?4?Detection about the concentration of Zn²⁺.Compared with the normal rats,the concentrations of Zn²⁺ were detected by the zinc ions kit in the blood and hippocampus of the model rats.?5?Detection about the biochemical indicators.Compared with the normal rats,zinc transporters?Zn T3?,neurotransmitters?Glu?and receptors?GABA-A,NMDA-NR2?were detected by the ELISA kit in hippocampus of the model rats.Main results 1.Behavioral tests:?1?the open field test: compared with the normal group,the number of squares crossing and standing times were significantly reduced in model group?P < 0.01?,suggesting that activity and exploration of the former were decreased;?2?the elevated plus maze: compared with the normal group,the number of both the opening and closed arms was significantly reduced?P < 0.01?,while the time percentages in the closed arms significantly increased?P < 0.01?in model group,suggesting that the rats in the model group showed decreased activity and increased anxiety;?3?space experiment of Morris water maze: compared with the normal group,numbers of the platform crossing and time percentages into the target quadrant were significantly reduced?P < 0.01?,suggesting that the spatial learning and memory ability were damaged in model group.2.Pathological Study:?1?In normal group,the morphology and distribution of cells in cerebral cortex and areas of CA1,CA2,CA3,dentate gyrus in hippocampus were regular,the nucleoli were clear and the Nissl bodies were rich in cytoplasm;?2?In model group,the morphology and distribution of cells in cerebral cortex were regular,there were no significant pathological changes,too;?3?In model group,the morphology and distribution of cells in areas of CA1,CA3 in hippocampus were irregular,gaps between the cells were increased and we could see some physaliferous cells,especially in area of CA3.?4?In model group,the morphology and distribution of cells in area of CA2 in hippocampus were regular?5?In model group,we could see some cells arranged loosely,gaps between the cells were increased and the numbers of the Nissl Body were decreased.3.Detection about the concentration of Zn²⁺: the concentration of Zn²⁺ in the blood has not changed significantly while it has decreased in the hippocampus in PTSD rats.4.Detection about the biochemical indicators: The concentration of Zn T3 transport protein was decreased,while the NMDA?NR2?receptor,GABA-A receptor,glutamate levels were increased in hippocampus.Conclusions?1?The model of PTSD rats has been established successfully;?2?In model group,pathological changes were not showed obviously in cerebral cortex and area of CA2 in hippocampus,while areas of CA1,CA3 and dentate in hippocampus showed pathological damages in different degrees;?3?The hippocampus of PTSD rats showed pathological damages in different degrees,and these damages had selectivity in areas,which may lead to the spatial learning and memory impairment;.?4?With the help of Zn T3,the free Zn²⁺ in the hippocampus may enter into the nerve cells through NMDA?NR2?receptor,GABA-A receptor channel,and then the Zn²⁺shows great damage to the hippocampus,causes spatial memory deficits and cognitive impairment.