Mechanism Of The Expression Of Glucocorticoid Receptor In The Hippocampus Of Rat Model Of Depression By Chronic Stress

Objective: This research aimed to explore the mechanism of HPA axis hyperfunction and hippocampus damage in depression by chronic stress. To observe the behaviors of rats, morphological changes of adrenal cortex and hippocampal neuron after different chronic stress, while measure the number and expression of glucocorticoid receptor in hippocampus, and the effect of following mifepristone treatment, thus to discover the possible etiopathogenisis on how chronic stress induced depression and find some clues to new treatment medicine.Methods: Designated mature SD male rat from Soochow university SPF animal centre and divided stochastically into the normal control group(NC), the mental stress group(MS), the glucocorticoid group(CO), MS group received 21 days of chronic immobilization stress, and CO group were injected glucocorticoid 20 mg/kg. d for 21 days, at the second weekend, Half of MS and CO groups were selected randomly as MS+RU group and CO+RU group, which both followed by mifepristone 54 mg/kg. d for 7 days. After the models succeeded, adrenal gland and brain were put into paraform for further study, paraffin section and immunohistochemistry for GR were necessary to be made. Moreover, using reverse transcription-polymerase chain reaction (RT-PCR) method to measure the expression of GRmRNA in hippocampus. Utilizing ANOVA and t test to analyze all collected data in SPSS13.0.Results: (1) The body weight gained, 24 h total intake and the consumption of 1 % sucrose intake in MS group and CO group remarkably reduced, and also showed a decrease in open-field test(P<0.01), the rat model of depression has been established successfully on 21st day. (2) Adrenal cortex obviously thickened in both MS group and CO group, especially the fascicular zone cells, which could explain the accentuation of adrenal gland function. (3) hippocampus neurons decreased in MS group and CO group, CA3 subregion most obvious, following by CA1,CA2, then DG subregion. (4) The positive number of GR expression in hippocampus neuron was lower than NC group after stress (P<0.01). (5) The present results demonstrated that the expression of GRmRNA in hippocampus significantly decreased compared to NC rats (P<0.01). (6) However, after mifepristone treatment, the body weight gained and the consumption of 1 % sucrose intake improved significantly (P<0.01). (7) The positive number of GR expression in hippocampus neuron increased obviously after mifepristone injection (P<0.01). (8) The expression of GRmRNA increased in MS+RU group and CO+RU group and had the significant difference compared with the MS group and the CO group (P<0.01).Conclusion: Chronic immobilization stress and glucocorticoid injection respectively established stress models to study depression successfully. Adrenal gland cortex accentuation and hippocampus damage, especially in CA3, were conspicuous in stress rat. The decrease number of GR and the dysfunction expression of GRmRNA in hippocampus involved in the pathogenesis of stress induced depression, and mifepristone which can improve the expression of GR, might play an important role in depression.