Dataset Information

Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice.

ABSTRACT:

Background

Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice.

Methods

The antidepressant-like effects of andrographolide in mice were explored in a forced swim test, tail suspension test, and chronic unpredictable mild stress model of depression. Western blotting and immunofluorescence were further performed to assess the effects of chronic unpredictable mild stress and andrographolide on the brain-derived neurotrophic factor signalling cascade and hippocampal neurogenesis. Moreover, a pharmacological inhibitor (K252a) and a lentiviral-short hairpin RNA (LV-TrkB-shRNA) were used to clarify the antidepressant-like mechanism of andrographolide.

Results

Andrographolide exhibited antidepressant-like potential in the forced swim test and tail suspension test without influencing the locomotor activity of mice. Repeated andrographolide treatment not only produced significant antidepressant-like effects in the chronic unpredictable mild stress model but also prevented the decreasing effects of chronic unpredictable mild stress on hippocampal brain-derived neurotrophic factor signalling and neurogenesis in mice. Importantly, blockade of the hippocampal brain-derived neurotrophic factor system by K252a and TrkB-shRNA fully abolished the antidepressant-like effects of andrographolide in mice.

Conclusions

Andrographolide exerts antidepressant-like effects in mice via promoting the hippocampal brain-derived neurotrophic factor signalling cascade.

SUBMITTER: Zhang JJ

PROVIDER: S-EPMC6754737 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice.

Zhang Jing-Jing JJ Gao Ting-Ting TT Wang Yuan Y Wang Jin-Liang JL Guan Wei W Wang Ying-Jie YJ Wang Cheng-Niu CN Liu Jian-Feng JF Jiang Bo B

The international journal of neuropsychopharmacology 20190901 9

<h4>Background</h4>Major depressive disorder is a worldwide neuropsychiatric disorder associated with various symptoms, but current antidepressants used in clinical practice have various side effects and high failure rates. Andrographolide is the main bioactive ingredient of Andrographis paniculata and exhibits numerous pharmacological actions. This study aimed to evaluate the antidepressant-like effects of andrographolide in male C57BL/6J mice.<h4>Methods</h4>The antidepressant-like effects of ...[more]

PMID: 31181145

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Project description:BackgroundDepression is a serious psychiatric disorder that easily causes physical impairments and a high suicide rate. Monosialotetrahexosylganglioside is a crucial ganglioside for the central nervous system and has been reported to affect the function of the brain derived neurotrophic factor system. This study is aimed to evaluate whether monosialotetrahexosylganglioside has antidepressant-like effects.MethodsAntidepressant-like effects of monosialotetrahexosylganglioside were assessed in the chronic social defeat stress model of depression, and various behavioral tests were performed. Changes in the brain derived neurotrophic factor signaling pathway after chronic social defeat stress and monosialotetrahexosylganglioside treatment were also investigated. A tryptophan hydroxylase inhibitor and brain derived neurotrophic factor signaling inhibitors were used to determine the antidepressant mechanisms of monosialotetrahexosylganglioside.ResultsMonosialotetrahexosylganglioside administration significantly reversed the chronic social defeat stress-induced reduction of sucrose preference and social interaction in mice and also prevented the increased immobility time in the forced swim test and tail suspension test. In addition, monosialotetrahexosylganglioside completely ameliorated the stress-induced dysfunction of brain derived neurotrophic factor signaling cascade in the hippocampus and medial prefrontal cortex, 2 regions closely involved in the pathophysiology of depression. Furthermore, the usage of brain derived neurotrophic factor signaling cascade inhibitors, K252a and anti-brain derived neurotrophic factor antibody, each abolished the antidepressant-like effects of monosialotetrahexosylganglioside, while the usage of a serotonin system inhibitor did not.ConclusionsTaken together, our findings suggest that monosialotetrahexosylganglioside indeed has antidepressant-like effects, and these effects were mediated through the activation of brain derived neurotrophic factor signaling cascade.

Project description:Evidence suggests that the down-regulation of the signaling pathway involving brain-derived neurotrophic factor (BDNF), a molecular element known to regulate neuronal plasticity and survival, plays an important role in the pathogenesis of major depression. The restoration of BDNF activity induced by antidepressant treatment has been implicated in the antidepressant therapeutic mechanism. Because there is variability among patients with major depressive disorder in terms of response to antidepressant treatment and since genetic factors may contribute to this inter-individual variability in antidepressant response, pharmacogenetic studies have tested the associations between genetic polymorphisms in candidate genes related to antidepressant therapeutic action. In human BDNF gene, there is a common functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF. Because of the potentially important role of BDNF in the antidepressant mechanism, many pharmacogenetic studies have tested the association between this polymorphism and the antidepressant therapeutic response, but they have produced inconsistent results. A recent meta-analysis of eight studies, which included data from 1,115 subjects, suggested that the Val/Met carriers have increased antidepressant response in comparison to Val/Val homozygotes, particularly in the Asian population. The positive molecular heterosis effect (subjects heterozygous for a specific genetic polymorphism show a significantly greater effect) is compatible with animal studies showing that, although BDNF exerts an antidepressant effect, too much BDNF may have a detrimental effect on mood. Several recommendations are proposed for future antidepressant pharmacogenetic studies of BDNF, including the consideration of multiple polymorphisms and a haplotype approach, gene-gene interaction, a single antidepressant regimen, controlling for age and gender interactions, and pharmacogenetic effects on specific depressive symptom-clusters.

Dataset Information

Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice.

Background

Methods

Results

Conclusions

Publications

Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice.

Similar Datasets

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