PMID- 36614017 OWN - NLM STAT- MEDLINE DCOM- 20230112 LR - 20230112 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 1 DP - 2022 Dec 29 TI - Novel Antidepressant Mechanism of Ginsenoside Rg1 in Regulating the Dysfunction of the Glutamatergic System in Astrocytes. LID - 10.3390/ijms24010575 [doi] LID - 575 AB - Ginsenoside Rg1, a traditional Chinese medicine monomer, has been shown to have antidepressant effects. We previously found that Rg1 exerts antidepressant effects by improving the gap junction channels (GJCs) dysfunction; however, the downstream mechanisms through which Rg1 ameliorates GJC dysfunction remain unclear. Since hemichannels directly release glutamate, GJC dysfunction decreases the expression levels of glutamate transporters in astrocytes, and glutamatergic system dysfunction plays an essential role in the pathogenesis of depression. The glutamatergic system may be a potential downstream target of Rg1 that exerts antidepressant effects. Therefore, in this study, we aimed to determine the downstream mechanisms by which Rg1 ameliorated GJC dysfunction and exerted its antidepressant effects. Corticosterone (CORT) is used to mimic high glucocorticoid levels in patients with depression in vitro. Primary cortical astrocytes were isolated and phosphorylation of connexin43 (Cx43) as well as the functions of hemichannels, GJCs, and the glutamatergic system were evaluated after drug treatment. Rg1 pretreatment reversed the anomalous activation of Cx43 phosphorylation as well as the dysfunction of hemichannels, GJCs, and the glutamatergic system induced by CORT. These results suggest that Rg1 can ameliorate CORT-induced dysfunction of the glutamatergic system in astrocytes by potentially reducing Cx43 phosphorylation and inhibiting opening of hemichannels, thereby improving GJC dysfunction. FAU - Zhang, Ningning AU - Zhang N AD - 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, China. FAU - Jiang, Hong AU - Jiang H AD - 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, China. FAU - Wang, Huiqin AU - Wang H AD - School of Pharmacy, Hunan University of Traditional Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, China. FAU - Wang, Yating AU - Wang Y AD - Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China. FAU - Peng, Ye AU - Peng Y AD - School of Pharmacy, Hunan University of Traditional Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, China. FAU - Liu, Yangbo AU - Liu Y AD - School of Pharmacy, Hunan University of Traditional Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, China. FAU - Xia, Congyuan AU - Xia C AD - 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, China. FAU - Yan, Xu AU - Yan X AD - 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, China. FAU - Chu, Shifeng AU - Chu S AD - 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, China. FAU - Zhang, Yi AU - Zhang Y AUID- ORCID: 0000-0002-7422-8206 AD - Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China. FAU - Wang, Zhenzhen AU - Wang Z AUID- ORCID: 0000-0002-2330-2277 AD - 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, China. FAU - Chen, Naihong AU - Chen N AUID- ORCID: 0000-0001-6354-7853 AD - 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, China. AD - School of Pharmacy, Hunan University of Traditional Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, China. LA - eng GR - 82130109, 82274127, 81773924, 81573636/National Natural Science Foundation of China/ PT - Journal Article DEP - 20221229 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antidepressive Agents) RN - 0 (Connexin 43) RN - W980KJ009P (Corticosterone) RN - PJ788634QY (ginsenoside Rg1) RN - 0 (Ginsenosides) RN - 0 (Glutamates) SB - IM MH - Antidepressive Agents/pharmacology MH - Astrocytes/metabolism MH - *Connexin 43/metabolism MH - Corticosterone/metabolism MH - *Ginsenosides/therapeutic use MH - Glutamates/metabolism MH - Animals PMC - PMC9820673 OTO - NOTNLM OT - Cx43 OT - astrocytes OT - depression OT - gap junction channel OT - ginsenoside Rg1 OT - glutamate OT - hemichannel COIS- The authors declare no potential conflict of interest. EDAT- 2023/01/09 06:00 MHDA- 2023/01/11 06:00 PMCR- 2022/12/29 CRDT- 2023/01/08 01:24 PHST- 2022/09/26 00:00 [received] PHST- 2022/12/19 00:00 [revised] PHST- 2022/12/23 00:00 [accepted] PHST- 2023/01/08 01:24 [entrez] PHST- 2023/01/09 06:00 [pubmed] PHST- 2023/01/11 06:00 [medline] PHST- 2022/12/29 00:00 [pmc-release] AID - ijms24010575 [pii] AID - ijms-24-00575 [pii] AID - 10.3390/ijms24010575 [doi] PST - epublish SO - Int J Mol Sci. 2022 Dec 29;24(1):575. doi: 10.3390/ijms24010575.