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

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.

Oleuropein reduces anxiety-like responses by activating of serotonergic and neuropeptide Y (NPY)-ergic systems in a rat model of post-traumatic stress disorder

“…Thus, OLE may not modulate the central adrenergic system, and may indirectly alter catecholamine synthesis in the brain. Many studies have suggested that PTSD can affect the neuronal circuitry and cause an imbalance in neurotransmitters, intensifying anxiety (Ebenezer et al 2016 ). We hypothesized that SPS-induced anxiety-like symptoms would be associated with central 5-HT dysfunction.…”

Metabolism, Metabolomics, and Inflammation in Posttraumatic Stress Disorder

“…Selective serotonin reuptake inhibitors, including fluoxetine, are considered firstline medication treatments for human PTSD. Using the footshock fear-conditioning mouse model (67), administration of fluoxetine improved PTSD symptoms while concurrently inhibiting stress-induced inflammatory gene expression (65,71).…”

Current Developments on Anti-Inflammatory Natural Medicines

“…Blueberry contains a significant amount of flavonoids, specially anthocyanins, which are the active components possessing antiinflammatory action. Studies revealed that blueberry-enriched diet normalized the enhanced levels free radicals, gene and protein expression of inflammatory cytokines in post-traumatic stress disorder in rats [53]. Johnson et al evaluated anti-inflammatory effect of anthocyanins and proanthocyanidins from fermented blueberryblackberry beverages and observed that the compounds reduced LPS-induced inflammation through NF-κB-mediated pathway in macrophages of mouse [54].…”