The Anti-Inflammatory Effects of Blueberries in an Animal Model of Post-Traumatic Stress Disorder (PTSD)

PLoS One. 2016 Sep 7;11(9):e0160923. doi: 10.1371/journal.pone.0160923. eCollection 2016.

Abstract

Post-traumatic stress disorder (PTSD) is a trauma and stressor-related disorder that results in a prolonged stress response. It is associated with increased oxidative stress and inflammation in the prefrontal cortex (PFC) and hippocampus (HC). The only approved therapy for PTSD is selective serotonin re-uptake inhibitors (SSRIs), but their efficacy is marginal. Recently, we demonstrated that over-production of norepinephrine (NE) as the possible reason for the lack of efficacy of SSRIs. Hence, there is a need for novel therapeutic approaches for the treatment of PTSD. In this study, we investigated the anti-inflammatory role of blueberries in modulating inflammatory markers and neurotransmitter levels in PTSD. Rats were fed either a blueberry enriched (2%) or a control diet. Rats were exposed to cats for one hour on days 1 and 11 of a 31-day schedule to simulate traumatic conditions. The rats were also subjected to psychosocial stress via daily cage cohort changes. At the end of the study, the rats were euthanized and the PFC and HC were isolated. Monoamines were measured by high-performance liquid chromatography. Reactive oxygen species (ROS), gene and protein expression levels of inflammatory cytokines were also measured. In our PTSD model, NE levels were increased and 5-HT levels were decreased when compared to control. In contrast, a blueberry enriched diet increased 5-HT without affecting NE levels. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also studied and they confirmed our findings. The enhanced levels free radicals, gene and protein expression of inflammatory cytokines seen in the PTSD group were normalized with a blueberry enriched diet. Decreased anxiety in this group was shown by improved performance on the elevated plus-maze. These findings indicate blueberries can attenuate oxidative stress and inflammation and restore neurotransmitter imbalances in a rat model of PTSD.

MeSH terms

  • Animals
  • Blueberry Plants*
  • Chromatography, High Pressure Liquid
  • Disease Models, Animal
  • Hippocampus / drug effects*
  • Humans
  • Inflammation / diet therapy*
  • Inflammation / genetics
  • Inflammation / physiopathology
  • Neurotransmitter Agents
  • Norepinephrine / metabolism
  • Oxidative Stress / drug effects
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / physiopathology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / administration & dosage
  • Stress Disorders, Post-Traumatic / diet therapy*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Tryptophan Hydroxylase

Substances

  • Neurotransmitter Agents
  • Reactive Oxygen Species
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Tryptophan Hydroxylase
  • Norepinephrine

Grant support

This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Research Program 2014 under Award No. W81XWH-15-1-0061 and United States Highbush Blueberry Council for JF. The opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense or United States Highbush Blueberry Council. There was no additional external funding received for this study.