title: Ginsenoside Rg1-induced antidepressant effects involve the protection of astrocyte gap junctions within the prefrontal cortex.
abstract: Ginsenoside Rg1 (Rg1) exhibits antidepressant-like activity by increasing neurogenesis and dendritic spine density without discernible side effects. However, the molecular mechanisms underlying Rg1 antidepressant activity remain poorly understood. As the dysfunction of gap junctions between astrocytes in the prefrontal cortex (PFC) is implicated in major depression disorder, the aim of this study was to investigate the effects of Rg1 on astrocyte gap junctions in the PFC. Rats exposed to chronic unpredictable stress (CUS) were administered Rg1 (5, 10, and 20mg/kg) for 28days and analyzed for depressive symptoms using the sucrose preference and forced swimming tests. Functional and morphological changes of gap junction channels in the PFC were evaluated using dye transfer and electron microscopy, respectively. The expression of connexin 43 (Cx43) was analyzed by western blotting. Rg1 markedly alleviated depression-like behavior in rats. Long-term Rg1 treatment of CUS-exposed rats also significantly prevented the decrease in dye diffusion and improved the ultrastructure of astrocyte gap junctions in the PFC, indicating beneficial effects on the functional activity of gap junction channels in the brain. In addition, Rg1 upregulated Cx43 expression in the PFC reduced by CUS exposure, which significantly correlated with its antidepressant-like effects. The results demonstrate that Rg1-induced antidepressant effects are might be mediated, in part, by protecting astrocyte gap junctions within the prefrontal cortex.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors.forename: Can
authors.initials: C
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Lou
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Man-Tong
authors.initials: MT
authors.lastname: Tian
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Du
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawahata
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamakuni
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China. Electronic address: chennh@imm.ac.cn.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China; Hebei University of Science and Technology, Shijiazhuang, Hebei 050018, PR China. Electronic address: zhangds2011@126.com.
authors.forename: Dan-Shen
authors.initials: DS
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D018031:Connexin 43 / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects* / Q000648:ultrastructure; D036145:Ginsenosides / Q000494:pharmacology*; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: D000199:Actins; D000928:Antidepressive Agents; D018031:Connexin 43; D036145:Ginsenosides; D007546:Isoquinolines; D013395:Sucrose; C017475:lucifer yellow; C035054:ginsenoside Rg1
keywords: Chronic unpredictable stress; Connexin 43; Depression; Gap junction; Ginsenoside Rg1