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http://dx.doi.org/10.1016/j.jgr.2021.03.005

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)
Publication Information
Journal of Ginseng Research / v.46, no.3, 2022 , pp. 376-386 More about this Journal
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
Ginsenoside Rb1; Depression; miR-134; BDNF-TrkB signaling; Synaptic plasticity;
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