The Role And Mechanism Of Ginsenoside Rg1 Neuroprotection Effects On The Development Of Depression

Introduction Depression is a common neuropsychiatric disorder with great harm to behavioral and emotional health in human. It has been associated with a wide range of structural and functional changes within specific brain regions, but the pathological mechanisms have not yet been completely understood. Brain researches have shown that the structural and functional impairment of the brain limbic system in patients with major depression. The ginsenoside Rgl has been shown to exert a number of neuroprotective effects as demonstrated in various in vivo and in vitro studies. However, little information is available regarding the site and mechanisms of ginsenoside Rgl in promoting antidepressant effects. The present study aimed to investigate the lateral amygdala synaptic plasticity formation change on chronic unpredictable mild stress (CUMS) which should be taken by means of behavioral science, biochemistry and molecular biology technology in depressive behavior. And further study about the neuroprotective effects and signal pathway of ginsenoside Rgl on depression-like behavior should be discussed.Objectives 1.To determine the ccurrence and development of neural plasticity changes in chronic stress induced depression by chronic unpredictable mild stress (CUMS) model.2. Study the role of the SIRT1-CREB-BDNF signal system in the regulation of neural plasticity in rat.3. Study the mechanism of ginsenoside Rgl through SIRT1-CREB-BDNF signal pathway to improve the depression symptoms.Methods The Wistar rats were randomly divided into blank control group, CUMS group, ginsenoside treatment group (G-Rgl+CUMS) and solvent treatment group(NaCl 0.9%+CUMS). Except for the control group, the other three groups were treated with chronic unpredictable mild stress stimulation for six weeks. Rats were subjected to a set of behavioral tests that included open-field test, sucrose preference test and forced swimming test after treatments. Western Blot and immunofluorescence were used to detect the expression of SIRT1, CREB, BDNF and synapse associated proteins PSD-95, synaptophysin (SYP), and the changes of the protein levels. The changes of gene expression levels were measured by RT-PCR technique.Result 1.Compared with the blank control group, the weight gain of CUMS rats was relatively slow with the loss of pleasure and the increase in despair, resulting in depression-like behavior.2. Western Blot and immunofluorescence showed that the protein expression of SIRT1, CREB, BDNF, PSD-95, SYP decreased in CUMS group 3. RT-PCR showed that the DNA expression of SIRT1, CREB, BDNF, PSD-95, SYP decreased in CUMS group.4. Compared with CUMS group, rats with depression-like behavior have been improved with protein and DNA expression in ginsenoside Rgl group.Conclusion Taken together, the results of the present study demonstrate that ginsenoside Rgl exhibits antidepressant-like effects against CUMS-induced depression. This amelioration of depression-like behaviors by ginsenoside Rg1 appears to be mediated, at least in part, by a CREB-regulated increase of BDNF, PSD-95, SYP expression in the amygdala of rats. Therefore, these findings reveal the therapeutic potential of ginsenoside Rgl for use in clinical trials in the treatment of depression.