Ginseng total saponins rescue susceptibility to adult depression-like behaviors in mice induced by early-life stress via regulating CREB/BDNF/TrkB signaling

ABSTRACT

In this study, mice undergoing either short maternal separation (MS) or long MS during early postnatal life and then experiencing chronic unpredictable mild stress (CUMS) in adulthood were established to explore the critical mechanism of the ginseng total saponins (GTS), extractions of ginseng, on early-life stress (ELS) and subsequent susceptibility to depression-like behaviors in adulthood. The behavioral assessment confirmed that GTS could reduce susceptible effects on mice induced by ELS to develop subsequent adult depression-like behaviors. The epigenetic changes of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-related kinase B (TrkB), and the downstream target cAMP-response element-binding protein (CREB) in the hippocampal tissue were elevated after GTS treatment. Interestingly, the inhibitor of TrKB, K252a further verified the above findings. All evidence showed that GTS had potential neuroprotective effects due to GTS could restore behavioral abnormalities and alter hippocampal protein levels via the CREB-BDNF-TrkB pathway, thereby ameliorating depression-like behaviors induced by MS.

KEYWORDS:

• Ginseng total saponins
• early-life stress
• chronic unpredictable mild stress
• susceptibility
• CREB/BDNF/TrkB pathway

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

YB and LY conceived and designed this study. YW, PL, WL, and JM helped with the experiment. YG helped with the mechanism figures. BZ analyzed the data. YY revised the manuscript.

Data availability statement

All data are available from the corresponding authors on reasonable request.

Additional information

Funding

This work was supported by the Natural Science Foundation of Jiangsu Province [BK20211297] and the 333 High-Level Talents Cultivation Project of Jiangsu Province.