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.

Autor:	Wang G; College of Pharmacy, Jinan University, Guangzhou, China., An T; College of Pharmacy, Jinan University, Guangzhou, China., Lei C; College of Pharmacy, Jinan University, Guangzhou, China., Zhu X; College of Traditional Chinese Medicine, Jinan University, Guangzhou, China.; Department of the First Affiliated Hospital, Jinan University, Guangzhou, China., Yang L; College of Pharmacy, Jinan University, Guangzhou, China., Zhang L; College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, China., Zhang R; College of Pharmacy, Jinan University, Guangzhou, China.
Jazyk:	angličtina
Zdroj:	Journal of ginseng research [J Ginseng Res] 2022 May; Vol. 46 (3), pp. 376-386. Date of Electronic Publication: 2021 Mar 20.
DOI:	10.1016/j.jgr.2021.03.005
Abstrakt:	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 3'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. Competing Interests: The authors declare that they have no competing interests. (© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)
Databáze:	MEDLINE
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