Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 75, Issue -, Pages 183-191Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2016.09.006
Keywords
Depression Chronic unpredictable stress; Ginsenoside Rg1; Gap junction; Connexin 43
Funding
- National Natural Science Foundation of China [81274122, U1402221, 81573636, 81560663]
- Beijing Natural Science Foundation [7131013, 7142115]
- Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study [BZ0150]
- PUMC Youth Fund [3332016058]
- Fundamental Research Funds for the Central Universities [2014RC03, 2016R050002]
- Key Research and Development Project of Hunan Province [2015SK2029-1]
- Scientific Research Foundation of the Higher Education Institutions of Hunan Province [15K091]
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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 20 mg/kg) for 28 days 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.(C) 2016 Elsevier Inc. All rights reserved.
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