Influence Of Chronic Stress To Neuron Proliferation And Apoptosis In The Hippocampus Of Rats And The Intervention Of Fluoxetine

Introduction and ObjectiveDue to subjective, unstable and equivocal results, the reliable evaluation of mental injury is a difficult issue in forensic psychiatry. The experiments adopted the forced swimming as stress animal model, which is used to observe the behavior, weight and endosecretion of rats, to evaluate effect of stress. To explore the influence of cell proliferation and apoptosis with chronic stress, this research determined the cell proliferation and apoptosis of hippocamp neuron through the immunohistochemistry and Hoechst fluorescein stain. Meanwhile, it was used the fluoxetion as a classic SSRI thymoleptics, to explore the intervention of behavior, endosecretion ,cell proliferation and apoptosis of chronic stress rats,to provide the theory according for the medicolegal investigation, clinical treatment and preservation of PTSD.Materials and Method24 adult male Sprague-Dawley rats were randomly divided into 4 groups (n=6 each group): control group, 4-week stress group, saline with 4-week stress group, fluoxetine with 4-week stress group. Forced swimming test was used as stressor. Behaviors were tested with the open-field test and rats'body weights were measured at the beginning and the end of stress. Corticosterone level was measured by enzyme linked immunosorbent assay (ELISA). The cell proliferation of hippocampus dentate gyrus was measured by PCNA immunohistochemistry. After chronic stress, the result of the numbers of neuron proliferation and apoptosis were given by correlation analysis with the behavior of rat and the concentration of corticosterone. The data were analyzed by one-way analysis of variance (ANOVA),LSD and Dunnett T3, t test with EXCEL2003 and SPSS13.0 for Windows. The consequence was expressed by mean±standard deviation ( x±SD). Correlation analysis was used by the way of Pearson.The significant discrepancy was P<0.05.Results(1) Behavior, weight and corticosterone changes: The number of crossing in control group and fluoxetine with 4-week stress group were significantly higher than 4-week stress group and saline with 4-week stress group; The detention time of central grille in 4-week stress group and saline with 4-week stress group were higher than control group and fluoxetine with 4-week stress group; The number of rear in 4-week stress group and saline with 4-week stress group were significantly lower than control group and fluoxetine with 4-week stress group, p<0.01; The weight of rats in control group was significantly higher than other groups, p<0.01; The level of serum cortisone in control group was significantly lower than other groups, p<0.01.(2) The influence of chronic stress on the proliferation of hippocampus cell in dentate gyrus: the index of PCNA and its number of positive cell in dentate gyrus of 4-week stress group were significantly lower than control group, p<0.01.(3) The influence of chronic stress on the cell apoptosis in hippocampus: the number of apoptosis cell in the area of CA1, CA3 and dentate gyrus in 4-week stress group were significantly higher than the control group, p<0.01.(4) The influence of fluoxetine on the proliferation and apoptosis of cell of chronic-stress rats: the index of PCNA and its number of positive cell in the fluoxetine with 4-week stress group were significantly higher than 4-week stress group, p<0.01, but there was no significantly difference with the control group; The number of apoptosis cell in the area of CA1 and CA3 of fluoxetine with 4-week stress group were significantly lower than 4-week stress group, p<0.01, had no significantly with control group; The number of apoptosis cell in dentate gyrus of fluoxetine with 4-week stress group were higher than 4-week stress group, but lower than control group, p<0.01.(5) The numbers of neuron proliferation have positive correlation with the number of the creep and rear. They have a tendency of decrease, accompanied with the increase of the concentration of corticosterone and the detention time of central grille. The numbers of neuron apoptosis have negative correlation with the number of the creep and rear, positive correlation with the detention time of central grille. They have a tendency of increase, accompanied with the increase of the concentration of corticosterone.Conclusions(1) The movement of chronic stress rats were relatively passive, accompanied with losing weight and the rise of corticosterone,which is similar with the depressive disorder and PTSD of mankind. (2) The results of behavior and corticosterone showed that the forced swimming experiment was a valuable chronic stress model.(3) The nerve cell's proliferation ability in hippocampus were weakened and the number of apoptosis cell were increased after the chronic stress.(4) Fluoxetine, as typical SSRI antidepressants, can prevent or reverse the lower cell-proliferation ability, and decrease the number of apoptosis cell in hippocampus.(5) The neuron proliferation and apoptosis in hippocampus have dependability with behavior and level of endocrine secretion.Accompanied with the increase of neuron proliferation in hippocampus, the activities of rats increase and the concentration of corticosterone decrease.Accompanied with the increase of neuron apoptosis in hippocampus, the activities of rats decrease and the concentration of corticosterone increase.