Study On The Dynamic Changes Of Glucocorticoid Receptor And Morphological Structure Of Hippocampus In The Rat Model Of Depression

Objective: The chronic unpredictable mild stress(CUMS)and social defeat stress(SDS) rat model of depression were established to analyze and compare the rats behavior changes dynamically in order to analyze and compare the feasibility and validity of the two models. Based on that,this paper aims to explore the change of the expression of glucocorticoid receptor(GR) in the hippocampus of rat model of depression by CUMS. This study further aims to explore the changes of the expression of glucocorticoid receptor(GR) in the hippocampus of rats model of depression by CUMS and SDS. Providing the basis and reference for the related mechanism of depression.Methods: 1.30 SD rats were randomly devised into 3 groups,control group、the CUMS group and SDS group with 10 in each group. The control group was fed according to the standard and was not treated any stress. Compared with control group, depressive group were handled 4 weeks by CUMS and SDS group. Body weight, Morris water maze test and percentage of sugar consumption were tested among the three groups before and after trial until the end of fourth week.2.A rat model of depression was established with the CUMS method.The hippocampus tissues in rats 2 and 4 and 6 weeks after stress were extracted a nd the normal hippocampus tissues used as control were collected.The express ions of GR in the hippocampus in each group were observed by the immunofl uorescent technology, using reverse transcription—polymerase chain reaction(RTPCR)method to measure the expression of GRm RNA in hippocampus.Using M RI and HE stain method to analyze the morphological and structural changes o f hippocampus of each group3.A rat model of depression was established with the CUMS method and SDS method.The hippocampus tissues in rats 2 and 4 weeks after stress were extracted and the normal hippocampus tissues used as control were collected.The expressions of GR in the hippocampus in each group were observed by the immunofluorescent technology, using reverse transcription—polymerase chain reaction(RT-PCR) method to measure the expression of GRmRNA in hippocampus.Using MRI and HE stain method to analyze the morphological and structural changes of hippocampus of each groupResults:1. The behavioral test results of the rat of depression of CUMS and SDS model : Compared with the control group, body weight, morris water maze test and the percentage of sugar consumption of the two stress groups changed significantly at the end of the second week(p< 0.05), and the change of the CUMS group was more significantly than the SDS group. The difference was statistically significant(p< 0.05), But the change of the SDS group was more significantly than the CUMS group at the end of the fourth week(p<0.05)2.Changes of hippocampal formation and glucocorticoid receptor(GR) expression in the rat model of depression induced by CUMS:(1) Under CLSM,GR-DyLight488 was green. GR was expressed in abundance in control group and fluorescence intensity was high. The expressive cell arranged closely and regularly. Compared with the control group, as the stress going on, the fluorescence intensity of GR expression in depressive hippocampus gradually weakened and the number of GR expression cell gradually fell, the morphological of hippocampus cell had become disorder. GR-positive cell number was significant lower than control group(P<0.01).)The expression of GRmRNA in the depressive group was significantly reduced compared to the control group(P<0.01).(2) The morphological and structural changes of hippocampus had the significant change in the depressive group. The hippocampus cells in rats 2 and 4 and 6 weeks after stress were arranged in disorder and the count decreased, the morphological and structural had become irregular.3.Changes of glucocorticoid receptor(GR) expression and the hippocampus morphology changes of effect brain in the rat model of depression induced by CUMS and SDS:(1)Under CLSM. GR of the hippocampus DG region cells were expressed in abundance before stress and fluorescence intensity was high. The hippocampus cell arranged closely and regularly.As the stress going on, the fluorescence intensity of GR expression in CUMS group and SDS group gradually weakened and the number of GR expression cell gradually fell, the morphological of hippocampus cell had become disorder at the end of the second week. CUMS group was significant lower than SDS group.But at the end of the fourth week,SDS group was significant lower than CUMS group. Compared with the CUMS group, GR immunoreactive cell counts and RT-PCR detection of GRmRNA in the hippocampus of SDS group showed a consistent change trend(P<0.05).(2) The morphological and structural changes of hippocampus had the significant change in CUMS group and SDS group. The morphological and structural of the hippocampus cells were arranged in disorder and the counts decreased at the end of the second week and the fourth week. Compared with the CUMS group, Changes of the SDS group showed a slower trend at the end of the second week and a faster trend at the end of the fourth week.Conclusion:1.The SDS and CUMS model can simulate the core symptoms of depression effectively, and two kinds of depression model behavior change are persistent.Compared to the CUMS model,the SDS model can make the animal to achieve a lasting and stable behavior,providing a more reliable and more objective selection for observation of depression physiological structure and biochemical changes dynamically2.The expression of glucocorticoid receptor(GR) in the hippocampus of rat model of depression by CUMS was decreased,resulting in hippocampal neurons damage.3. CUMS and SDS induced depression model rats perform a different rhythm change of hippocampal GR expression decreased and hippocampal morphological change. Compared with the CUMS model, SDS model can make the depression animal behavior to achieve a more lasting and stable state, and therefore combined with different types of stress models to investigate the changes of the expression of GR and the hippocampal structure,in order to further on a in-depth study of the pathogenesis of depression induced by different causes.