Abstract
Objectives
Gut has been known as the second brain and affects the brain via various pathways such as neurotransmitter modulation. We previously showed that water extract of Gastrodia elate Blume (WGE) exerts antidepression-like effect in forced swimming test. However, the impact of WGE on gut in subchronic and mild social defeat stress (sCSDS) model has not studied. Thus, we investigate the potential gut-brain linked mechanisms of WGE in relieving stress-induced depression-like behaviors which may result from the tryptophan (TRP) metabolism in mice subjected to sCSDS model.
Methods
C57/BL6J mice were divided into 6 groups: control (CTR), control with antibiotics (CTR + A), sCSDS, sCSDS with WGE (sCSDS + WGE), sCSDS with antibiotics (sCSDS + A) and sCSDS with antibiotics and WGE (sCSDS + A + WGE). Mice were administered 500 mg/kg body weight (BW) of WGE for 30 days and antibiotics by 10 ml/kg BW (0.1 mg/ml amphotericin B for the first 2 days, and then mixed with 5 mg/ml vancomycin, 10 mg/ml neomycin, 10 mg/ml metronidazol and 0.1 mg/ml amphotericin B for the next 28 days by gavage with ampicillin 1 mg/ml in drinking water), otherwise the sCSDS paradigm for 10 days, exclude the CTR groups. A social interaction test was conducted to assess the antidepression-like effects, while serum corticosterone (CORT) was tested as a stress indicator. Brain was isolated to dissect the TRP metabolism by using high performance liquid chromatography with electrochemical detection (HPLC-ECD).
Results
WGE significantly reversed the depression-like phenotypes, such as BW loss, social avoidance and stress index, serum CORT induced by sCSDS (P < 0.05). Whereas antibiotics administration elevated BW (P < 0.05). Treatment with antibiotics and WGE significantly increased social avoidance (P < 0.05). HPLC-ECD indicated WGE slightly normalized the 5-hydroxyindoleacetic acid (5-HIAA)/serotonin (5-HT) ratio, while antibiotics significantly decreased it, also significantly increased 5-HT and 5-HT/TRP ratio in prefrontal cortex (P < 0.05). In general, high levels of 5-HT in brain induced by sCSDS with antibiotics may linked to aggression, while WGE treatment reverse it.
Conclusions
The antidepression-like effects of WGE might be mediated by the regulation of TRP metabolism in gut-brain axis suggested to be a potential pathway to prevent depression.
Funding Sources
N/A.
Supporting Tables, Images and/or Graphs
Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress
