title: The effects of ginsenoside Rg1 on chronic stress induced depression-like behaviors, BDNF expression and the phosphorylation of PKA and CREB in rats.
abstract: Depression is a common neuropsychiatric disorder which has been associated with a wide range of structural and functional changes within specific brain regions. Ginsenoside Rg1 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 Rg1 in promoting antidepressant effects. The present study aimed to investigate the neuroprotective and ameliorating effects of ginsenoside Rg1 on depression-like behavior as induced by chronic unpredictable mild stress (CUMS). The results showed that CUMS was effective in producing depression-like behaviors in rats as indicated by decreased responses in sucrose preference and forced swim tests which were associated with ultrastructural changes in neurons within the amygdala. Moreover, levels of PKA and CREB phosphorylation and the expression of brain-derived neurotrophic factor (BDNF) were decreased in the amygdala of CUMS rats. Remarkably, chronic ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) treatment significantly ameliorated these behavioral and biochemical alterations associated with CUMS-induced depression. Taken together, the results of the present study demonstrate that ginsenoside Rg1 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 expression in the amygdala of rats. Therefore, these findings reveal the therapeutic potential of ginsenoside Rg1 for use in clinical trials in the treatment of depression.
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China; Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province 250012, PR China. Electronic address: shuyanyu@sdu.edu.cn.
authors.forename: S Y
authors.initials: SY
authors.lastname: Yu
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002908:Chronic Disease; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D036145:Ginsenosides; D017868:Cyclic AMP-Dependent Protein Kinases; C035054:ginsenoside Rg1
keywords: BDNF; amygdala; chronic unpredictable mild stress; depression; ginsenoside Rg1