| Research Background:Depression is a group symtom of mood disorders or the affective disorders taking despondently as a main symptom caused by each kind of reason. This common illness causes huge losses and damages to the human society. Damage of learning and memory ability is one of the symptoms of depression, the pathology of which is damage of hippocampus. Persistent high Glucocorticoid (GC) resulted from accentuation of HPA axis which is caused by stress of other reasons is generally considered to be the major causation of hippocampus damage.Objective:The present study was performed to explore the change of spatial learning and memory ability in depression model, and the effect of hign level GC on the cultured primary hippocampal cells and the possible mechanism.Method:The total rats were divided randomly into 2 groups:the stimulation group and its normal control group; The chronic miled unpredictable stress(CMUS) model of rat was adopted as the model of depression. Open-field test was used to detect the locomotion activity and HPLC-UV was employed to analyze the level of blood serum corticid. Measuring the latency and the ratio of time around the platform by Morris water Maze to evaluate the learning and memorry ability.. LTP and LTD were utilized to observe the change of synaptic plasticity in hippocampus neurons.. The changes of morphological structure in hippocampal CA 1 subregion was detected by frozen section technique. MTT assay was used to detect the survival rate of the hippocampal nerve cells treated by GC of different concentrations. By blocking GR, MR, NMDARs with antagonists, We detected the survival of hippocampal cells and concentration of Ca2+ in the cells under high dose of GC. The expression of NMDA receptor subunits (NR2A, NR2B), Bax, Bcl2, p-P38, p-Erkl/2 in hippocampal cells was observed by western blotting. MTT assay was used to detect the survival rate of SH-SY5Y cells treated by GC of different concentrations, and cell apoptosis was analysed by flow cytometry; Result:The results showed that the locomotion activity decreased extremely after CMUS, while the level of serum cortisol increased evidently. And the ability of spatial learning and memory decreased obviously. LTP and LTD data indicate the decline of study function in the depression groups. Simultaneity, hippocampal CA 1 subregion neurons were observed to be damaged. The survival rate of the hippocampal cells were decreased with increased GC. The injury effect of high dose of GC on cells was reversed by antagonists of GR and NMDARs. Expression of NR2A and NR2B were up regulated by high dose of GC, the ratio of Bax/Bcl2 was increased, and the phosphorylation of P38 and Erkl/2 were repressed. The survival rate of SH-SY5Y cells were decreased with increased GC concetrition. GC can induce cell apoptosis and change the cell cycle.Conclusion:These results suggested that stress may induce the increase of the level of cortisol, the damage of hippocampal neurons and the decline of synaptic plasticity among hippocampus neurons, which inhibits the ability of spatial learning and memory consolidation. There are several pathways related to the effect of high dose of GC on hippocampal cells injury, NMDARs and MAPK pathway may be the important participators. The study of SH-SY5 Y cells indicate that GC can induce cell apoptosis and may inhibit the cells from G1 phase to S phase. |
