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Antidepressant-like effects and memory enhancement of a herbal formula in mice exposed to chronic mild stress.

ABSTRACT: Shen Yuan Gan (SYG) is a Chinese herbal prescription composed of total saponins of Panax ginseng and total oligosaccharide esters of Polygala tenuifolia (2:1). Our previous studies have demonstrated that SYG has antidepressant-like effects in various mouse models of behavioral depression. The present study aimed to test whether SYG affected chronic mild stress (CMS)-induced depression and cognitive impairment in mice. We found that a 5-week CMS schedule induced significant degradation of the coat state, decreased sucrose intake in the sucrose-preference test, and increased the latency to feed in the noveltysuppressed feeding test. All of these CMS-induced changes were ameliorated by SYG (100 and 200 mg/kg) and fluoxetine (10 mg/kg). In addition, SYG restored the decreased monoamine neurotransmitter concentrations (serotonin, dopamine, norepinephrine and acetylcholine) induced by CMS in the prefrontal cortex. Interestingly, SYG ameliorated CMS-induced cognitive impairment in the step-through test, and increased the acetylcholine level in the prefrontal cortex. These results suggest that SYG has an antidepressant-like action and enhances cognition by modulating the serotonin, dopamine, norepinephrine, and acetylcholine levels in the prefrontal cortex.

SUBMITTER: Sun XP

PROVIDER: S-EPMC5562547 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Project description:Depression is a common mental disorder that presents a considerable challenge for public health. The natural product geniposide has neuroprotective effects on depression, but the underlying mechanism behind these effects had remained undefined. The present study was designed to investigate the role of microRNAs (miRs) in this mechanism. It studied mice with depression-like behavior established by exposure to chronic unpredictable mild stress (CUMS) for 2 months. The CUMS mice were intragastrically fed with geniposide at a dose of 10 ml/kg daily for two consecutive weeks. We monitored the depression-like behaviors of the CUMS mice by the forced swimming test (FST) and tail suspension test (TST). Then, we measured the cerebral expression of miR-298-5p and NADPH oxidase 1 (Nox1) mRNA in the CUMS mice by the RT-qPCR. The targeting relationship between miR-298-5p and Nox1 was evaluated by dual-luciferase reporter gene assay. The concentrations of adenosine triphosphate (ATP) and reactive oxygen species (ROS) were determined by the CellTiter-Glo® and flow cytometry, respectively. The mitochondrial membrane potential (MMP) was detected using JC-1 staining. Moreover, the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and TGF-β) was determined by ELISA, RT-qPCR, and western blot analysis. We found that miR-298-5p was poorly-expressed while Nox1 was highly-expressed in the brain tissues of the CUMS-induced mice. Intriguingly, Geniposide treatment reversed the behavioral abnormalities of CUMS mice, including shortened immobility time. Geniposide inhibited the Nox1 expression by increasing miR-298-5p levels. There were increased ATP content and MMP and reduced contents of ROS and inflammatory cytokines in the CUMS mice receiving geniposide treatment. Hence, this study revealed an antidepressant effect of geniposide on CUMS-induced depression-like behavior in mice by down-regulating the miR-298-5p-targeted Nox1. This highlights a novel candidate target for the treatment of depression.

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Antidepressant-like effects and memory enhancement of a herbal formula in mice exposed to chronic mild stress.

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