Dataset Information

Tetramethylpyrazine Produces Antidepressant-Like Effects in Mice Through Promotion of BDNF Signaling Pathway.

ABSTRACT:

Background

Current antidepressants are clinically effective only after several weeks of administration. Tetramethylpyrazine (TMP) is an identified component of Ligusticum wallichii with neuroprotective effects. Here, we investigated the antidepressant effects of TMP in mice models of depression.

Methods

Antidepressant effects of TMP were first detected in the forced swim test (FST) and tail suspension test (TST), and further assessed in the chronic social defeat stress (CSDS) model. Changes in the brain-derived neurotrophic factor (BDNF) signaling pathway and in hippocampal neurogenesis after CSDS and TMP treatment were then investigated. A tryptophan hydroxylase inhibitor and BDNF signaling inhibitors were also used to determine the mechanisms of TMP.

Results

TMP exhibited potent antidepressant effects in the FST and TST without affecting locomotor activity. TMP also prevented the CSDS-induced symptoms. Moreover, TMP completely restored the CSDS-induced decrease of BDNF signaling pathway and hippocampal neurogenesis. Furthermore, a blockade of the BDNF signaling pathway prevented the antidepressant effects of TMP, while TMP produced no influence on the monoaminergic system.

Conclusions

In conclusion, these data provide the first evidence that TMP has antidepressant effects, and this was mediated by promoting the BDNF signaling pathway.

SUBMITTER: Jiang B

PROVIDER: S-EPMC4571627 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

Tetramethylpyrazine Produces Antidepressant-Like Effects in Mice Through Promotion of BDNF Signaling Pathway.

Jiang Bo B Huang Chao C Chen Xiang-Fan XF Tong Li-Juan LJ Zhang Wei W

The international journal of neuropsychopharmacology 20150124 8

<h4>Background</h4>Current antidepressants are clinically effective only after several weeks of administration. Tetramethylpyrazine (TMP) is an identified component of Ligusticum wallichii with neuroprotective effects. Here, we investigated the antidepressant effects of TMP in mice models of depression.<h4>Methods</h4>Antidepressant effects of TMP were first detected in the forced swim test (FST) and tail suspension test (TST), and further assessed in the chronic social defeat stress (CSDS) mode ...[more]

PMID: 25618406

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Project description:SKF83959 stimulates the phospholipase Cβ/inositol phosphate 3 pathway, resulting in the activation of Ca(2+)/calmodulin-dependent kinase IIα, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine D5 receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase IIα pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal D5/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway.

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Dataset Information

Tetramethylpyrazine Produces Antidepressant-Like Effects in Mice Through Promotion of BDNF Signaling Pathway.

Background

Methods

Results

Conclusions

Publications

Tetramethylpyrazine Produces Antidepressant-Like Effects in Mice Through Promotion of BDNF Signaling Pathway.

Similar Datasets

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