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Stress-induced VIPergic activation mediates microbiota/Th17cell-dependent depressive-like behaviors.

Eva M Medina-Rodriguez1, Dongmei Han1, Shanie E Zeltzer1

  • 1Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, United States.

Brain, Behavior, and Immunity
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Chronic stress alters gut microbes via vasoactive intestinal peptide (VIP), increasing T helper 17 (Th17) cells and causing depression. Blocking interleukin-17A (IL-17A) reversed these effects, revealing a gut-brain axis target for depression.

Keywords:
DepressionMicrogliaTh17 cellVIP

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Area of Science:

  • Neuroscience
  • Microbiology
  • Immunology

Background:

  • Chronic stress negatively impacts gut physiology and can lead to psychiatric disorders.
  • The gut-brain axis is a key area for stress research, but mechanisms linking stress, gut microbes, and behavior are unclear.

Purpose of the Study:

  • To investigate the pathways through which stress influences gut microbial composition and modulates behavior.
  • To explore the role of vasoactive intestinal peptide (VIP) in stress-induced gut-brain axis alterations.

Main Methods:

  • Studied stress-induced changes in gut microbiota composition.
  • Investigated the role of VIP activation in stress responses.
  • Analyzed T helper 17 (Th17) cell infiltration and microglial activation in the hippocampus.
  • Examined the effects of neutralizing interleukin-17A (IL-17A) on stress-induced behaviors and neural changes.

Main Results:

  • VIP activation promoted stress-induced microbial changes.
  • These changes led to increased Th17 cell infiltration and microglial activation in the hippocampus, resulting in depressive-like behaviors.
  • Neutralizing IL-17A blocked depressive-like behaviors and reduced neuronal VIPergic and microglial activation.

Conclusions:

  • A crosstalk exists between intestinal VIP release and gut microbiota during stress, impacting the nervous system and microbiome.
  • Interleukin-17A is a key mediator in stress-induced depressive behaviors.
  • Targeting the VIP-gut microbiota-IL-17A axis offers potential therapeutic strategies for depression.