Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression

  • Wang, Guoli (College of Pharmacy, Jinan University) ;
  • An, Tianyue (College of Pharmacy, Jinan University) ;
  • Lei, Cong (College of Pharmacy, Jinan University) ;
  • Zhu, Xiaofeng (College of Traditional Chinese Medicine, Jinan University) ;
  • Yang, Li (College of Pharmacy, Jinan University) ;
  • Zhang, Lianxue (College of Chinese Medicinal Materials, Jilin Agricultural University) ;
  • Zhang, Ronghua (College of Pharmacy, Jinan University)
  • Received : 2020.11.12
  • Accepted : 2021.03.14
  • Published : 2022.05.01
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Abstract

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

Keywords

Acknowledgement

This work was supported by the National Natural Science Foundation of China (81903820), and National Key R&D Program of China (2018YFC2002500).

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