Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress

Neurosci Lett. 2016 Apr 8:618:159-166. doi: 10.1016/j.neulet.2016.03.003. Epub 2016 Mar 5.

Abstract

Sodium butyrate (NaB) has exhibited neuroprotective activity. This study aimed to explore that NaB exerts beneficial effects on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and its possible mechanisms. The behavioral tests including sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) and forced swimming test (FST) were to evaluate the antidepressant effects of NaB. Then changes of Nissl's body in the hippocampus, brain serotonin (5-HT) concentration, brain-derived neurotrophic factor (BDNF) and tight junctions (TJs) proteins level were assessed to explore the antidepressant mechanisms. Our results showed that CUMS caused significant depression-like behaviors, neuropathological changes, and decreased brain 5-HT concentration, TJs protein levels and BDNF expression in the hippocampus. However, NaB treatment significantly ameliorated behavioral deficits of the CUMS-induced mice, increased 5-HT concentration, increased BDNF expression, and up-regulated Occludin and zonula occludens-1(ZO-1) protein levels in the hippocampus, which demonstrated that NaB could partially restore CUMS-induced blood-brain barrier (BBB) impairments. Besides, the pathologic changes were alleviated. In conclusion, these results demonstrated that NaB significantly improved depression-like behaviors in CUMS-induced mice and its antidepressant actions might be related with, at least in part, the increasing brain 5-HT concentration and BDNF expression and restoring BBB impairments.

Keywords: 5-HT; Antidepressant; BDNF; Blood–brain barrier (BBB); Chronic unpredictable mild stress (CUMS); Sodium butyrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Blood-Brain Barrier / metabolism
  • Butyric Acid / pharmacology
  • Butyric Acid / therapeutic use*
  • Depression / drug therapy*
  • Depression / etiology
  • Depression / psychology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Serotonin / metabolism
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / psychology
  • Tight Junction Proteins / metabolism

Substances

  • Antidepressive Agents
  • Tight Junction Proteins
  • Butyric Acid
  • Serotonin