| In the present study, we examined the change of corticosterone concentration in blood serum and brain-derived neurotrophic factor (BDNF) in hippocampus(HP) and prefrontal cortex (PFC) in chronic stress induced-depression model mice, in order to probe into the antidepressive mechanism of Zhijujieyu- tang, a Chinese traditional herb prescription, and provide experimental evidence for clinical medication.Ninety two-month-old Kunming mice were randomly divided into six groups:the normal control group, the model group, the positive control (fluoxetine) group, the high, medium and low concentration groups of Zhijujieyu-tang. Mice depression models were established by chronic unpredictable stress methods (footshock, bondage, bondage+thermal stimulus, water deprivation, food deprivation, feeding in tilt cage and night lighting, unexpectedly given to mice, one method each day in twenty-one days). The behavioral changes of the depressive model mice were determined using Open-field,Tail-suspension and Morris Water Maze tests. The changes of morphological structure in HP and PFC of mice brain were observed by HE dye, the concentration changes of corticosterone (CORT) in blood serum were detected by enzyme linked immunosorbent assay (ELISA) and the expressional changes of BDNF were detected by immunohistochemical method.The results of this study are as follows:1. Compared with normal control group mice, the spontaneous activities and exploratory behaviors were remarkably decreased (P<0.01), and the despairing were remarkably increased in the model group mice (P<0.01). The spatial learning and memory in them were significantly decreased (P<0.05). Administration of Zhijujieyu-tang and fluoxetine remarkably improved depressive behavior in depression model mice(P<0.05).2.In the normal control group, the high, medium concentration group of Zhijujieyu-tang and fluoxetine group mice, the morphological results showed that there are lots of prick cells in hippocampal areas (CAland CA3), granular cells in Dentate gyrus(DG), they arrange tidily, administrative levels is compact. Cell nucleus are round and in the center of cells. They are deep blue and the cytoplasm is pink. The neurons in PFC have tidy shape, they arranged orderly, and they are dyed even.In low concentration group mice of Zhijujieyu-tang, the morphological results showed that Prick cells arrange more close, and its number has decreased, they are dyed lightly. Their shape is untidy.In the model group mice of Zhijujieyu-tang, the neural cells are irregular in shape and arrange untidily and laxly. The layers decreased obviously. Some cells have necrosed, some swollen. They are dyed uneven.3. The concentration of CORT in blood serum of depression model mice were significantly increased(P<0.01), compared with that of the mice in the normal control group. The three dosages of Zhijujieyu-tang, including the fluoxetine, can decrease the concentration of CORT in blood serum of depression model mice (P<0.01).4. Compared with the normal control group mice, the BDNF expression in CA1, CA3, DG regions of HP and PFC were significantly reduced in the model group mice (P<0.05). Zhijujieyu-tang medium and high dosages can improve the expression of BDNF(P<0.05)in CA1, CA3, DG regions of HP and PFC.Conclusions are as follows:1. The results of the behavior of the mice in different groups demonstrated that the three dosages of Zhijujieyu-tang have antidepressive effects, and there is significant effects between the medium dosage and fluoxetine.2. Zhijujieyu-tang have antidepressive effectiveness through decreasing the CORT concentration in blood serum of depressive mice, to enhance the negative feedback mechanism of HPA, and thus it can keep the balance of the internal environment homeostasis.3. Chronic stress cause significant reduction of BDNF expression in HP and PFC, and Zhijujieyu-tang can invert this change. Zhijujieyu-tang possesses a certain antidepressant-like property and its mechanism may be closely related to the up-regulation of BDNF expression in HP and PFC. |
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