Relationship Between The Antidepression Effect Of Vaproate And The Expression Of BDNF, NET,5-HTT And The Function Of HPA Aix In Rat Model

Objective：To demonstrate correlations of antidepressive effect of valproate withthe balance of oxidative stress/anti-oxidative stress, the expression ofBDNF, NET, and5-HTT, as well as the hypothalamic-pituitary-adrenal(HPA) axis function in the depressive rats leaded by CUMSMethod：1. Four following groups were established by divided80SD male ratsrandomly: control group (CG), the model group (MG), controlgroup-treated with300mg/kg/d valproate (VCG), and model group-treatedwith300mg/kg/d valproate (VMG). The rat depression model wasestablished by Chronically unpredicted mild stress (CUMS) with solitarycondition.2. The open-field test, sucrose consumption test, and force swimmingtest were used to evaluate the behavior changes of experimental rats.3. The pathological change of hippocampus slices with HE staining was observed by microscope.4. The malondialdehyde (MDA) level, activities of superoxidedismutase (SOD) and catalase (CAT) in serum and hippocampus weredetermined by biochemical methods. Radio-immunoassay was used todeterminate corticosterone (CORT) level in serum. The expressions ofBDNF in cortex, CRF in hypothalamus, and NET,5-HTT in hippocampus,were determined by Real-time Reverse transcription polymerase chainreaction (Real-time RT-PCR) and Western Blot (WB), respectively.Result：1. There was a significant decrease of locomotive activity in open-fieldand a significant increase of immobility time in force swimming test in MG,compared with CG. Though sucrose water consumption was decreased inMG group, there is no statistical significance. The depressive symptomscaused by CUMS were improved obviously by the treatment of valproate.However, the treatment of valproate had no significant influences onbehaviors of CG rats.2. Compared with CG rats, the MDA level was increased sharply, SODand CAT activities were clearly decreased in both serum and hippocampusof MG rats, and obvious promotion of serum CORT level and hypothalamusCRF expression were observed. At the same time, in comparison with CG,the reduced expression of BDNF,5-HTT and the risen NET expression inMG rats were determined. Treated with valproate distinctly suppressed the changes above.3. Compared with CG rats, clear hyperchromatism and karyopyknosisof hippocampal neurocytes were frequently observed in MG rats. Treatmentof valproate relieved the pathological damage to hippocampus.Conclusion:The anti-depressive effect of valproate may relate to improveoxidative stress, HPA axis function, and the expression of BDNF, NET and5-HTT.