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Coenzyme Q10 (CoQ10) is an endogenous lipid-soluble molecule with antioxidative and anti-inflammatory properties. Chronic environmental stress can induce neuroinflammation, leading to posttraumatic stress disorder (PTSD)-like behaviors and cognitive deficits. However, therapeutic options that achieve high efficacy with minimal adverse effects remain limited. Here, we investigated the effects of ubiquinol, the reduced form of CoQ10, administered via oral mucosal absorption on behavioral and molecular changes in mice subjected to social disruption (SD). Our results showed ubiquinol administration ameliorated SD-induced social avoidance and anxiety-like behaviors, accompanied by increased hippocampal brain-derived neurotrophic factor (BDNF) and decreased monoamine oxidases A and B (MAO-A and MAO-B). Additionally, ubiquinol suppressed SD-induced upregulation of inducible nitric oxide synthase (iNOS), lipocalin 2, and interleukin-6 (IL-6) in the hippocampus. In microglial cells, CoQ10 effectively attenuated lipopolysaccharide (LPS)-induced increases in iNOS and lipocalin 2 as well. Notably, CoQ10 restored the downregulated expression of peroxisome proliferator-activated receptor alpha (PPARα) observed under SD mice and microglial cells stimulated by LPS. The protective effects of ubiquinol were abrogated by inhibiting PPARα, resulting in reduced BDNF and elevated MAOs and pro-inflammatory mediators. Collectively, these findings demonstrate that ubiquinol mitigates neuroinflammation and behavioral impairments through PPARα-dependent mechanisms, thereby promoting BDNF expression and suppressing upregulation of monoamine oxidases in the hippocampus. The current study provides mechanistic insight into the potential therapeutic application of CoQ10 for chronic stress-induced behavioral and cognitive deficits. Show less

Post-traumatic stress disorder (PTSD) causes debilitating nightmares, flashbacks and anxiety stemming from a catastrophic, often life-threatening traumatic event. Originally described in soldiers exposed to the horrors of battle, PTSD is now recognized in civilian victims of assault, natural disasters and mass casualty events. Most people experiencing trauma do not develop PTSD, so understanding neurobiological mechanisms is crucial to predicting risk and developing targeted treatments. There have been many studies seeking to find biomarkers for PTSD, and their results have converged on several brain regions, molecular pathways and neuropsychological functions. In this review, we focus on selected findings about the glucocorticoid receptor (GR), the chaperone protein FKBP51 (FK506 binding protein 51), BDNF (brain-derived neurotrophic factor), fear memory reconsolidation and epigenetic regulation of gene expression in the hypothalamic-pituitary-adrenal (HPA) axis, amygdala and hippocampus. Together, these disparate aspects of brain function provide an emerging model for understanding the etiology and pathophysiology of PTSD. Avoidance of lethal threats is fundamental for survival, and this stringent evolutionary requirement has conserved many components of fear memory storage and behavioural response to danger. PTSD research can therefore rely on non-human animal model systems with better face and construct validity than most other psychiatric disorders. With this advantage, advances in PTSD biomarker identification are likely closer to clinical translation than in other mental illnesses. We attempt to highlight the most promising biomarkers that could be targeted by novel treatments and propose a map for future research work. Show less

Prenatal stress may lead to cognitive and behavioral dysfunction in the offspring. Large evidence has shown the deleterious effects of maternal stress on cognitive and behavioral functions of the offspring; however, the effect of paternal stress has not been well documented. In the present study, we aimed to investigate the effect of paternal stress (chronic electrical footshocks, post-traumatic stress disorder or PTSD-like model) on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) hippocampal level in both male and female offspring during adolescence. The father rat (stress-exposed) was exposed to three consecutive shocks in a fear conditioning apparatus for ten times during four weeks, in an uncertain and unpredictable schedule. Saline (0.5 mL) or lithium chloride (50 mg/kg) was intraperitoneally injected to male and female offspring during 21-41 postnatal day (PND). The results showed that paternal stress decreased locomotor activity in female offspring, and increased anxiety-like behavior in both male and female offspring, with more effect on females. Paternal stress also decreased pain subthreshold only in female offspring and impaired passive avoidance and spatial memory in both male and female offspring. Paternal stress also decreased BDNF expression level only in female offspring. However, lithium reversed most of the behavioral dysfunctions in rats' offspring with a history of paternal stress. We concluded that paternal stress significantly impairs cognitive and behavioral function in the offspring during adolescence, with more effect on females. Also, chronic lithium treatment may reverse the deleterious effects of paternal stress. Show less

Post-traumatic stress disorder (PTSD), in its partial or full forms, is frequently observed in military populations. It is therefore important to predict the risk of PTSD prior to deployment. Since elevated allostatic load markers have been described in PTSD, we investigated whether these alterations pre-exist before PTSD onset. Our objective was to explore the ability of four allostatic load markers (urinary and blood cortisol, BDNF and 8-iso-PGF2α) to predict partial/full PTSD onset after a 6-month deployment. We conducted a prospective study in a French military cohort deployed to Afghanistan. PTSD was assessed before (M After controlling for age, pre-deployment PCLS scores, and the number of missions, we found that elevated M Asymptomatic subjects at risk of partial/full PTSD exhibit a common pattern of hypothalamic-pituitary axis dysregulation, similar to that observed in established PTSD. Show less