Neuroendocrine Stress Induces Differential Oxidative Stress and Antioxidant Profiles between Proactive and Reactive...

Neuroendocrine stressors can disrupt the brain's redox equilibrium by generating high levels of reactive oxygen species (ROS) that lead to oxidative stress. The magnitude of the effect of neuroendocrine stressors on brain redox equilibrium can be influenced by many internal and external factors. To what extent the relationship between neuroendocrine and oxidative stress is modulated by an individual's stress coping style is only beginning to be understood. To explore this, we subjected proactive and reactive zebrafish to an acute novelty stressor and subsequently quantified changes in behavior and whole brain biomarkers of oxidative stress and antioxidants (DNA damage, total glutathione (GSH), glutathione ratio, oxygen radical absorbance capacity (ORAC), and superoxide dismutase (SOD). Stressed fish had significantly higher total glutathione, trends higher ORAC, DNA damage, and glutathione ratio, and trend for lower SOD levels compared to controls. In addition, individuals with a reactive stress coping style exhibited significantly higher levels of SOD and glutathione ratio, and a trend for ORAC compared to proactive individuals. From a principal component analysis, we also found that the reactive individuals had significantly higher PC1 scores (antioxidant axis) compared to the proactive, and a trend for stressed fish having higher PC1 scores than control. The oxidative stress axis (PC2) showed that the stressed fish had a significantly higher PC2 score relative to control fish. Our results show that neuroendocrine stress-induced disruption of redox equilibrium in the brain differs by stress coping style. Those with a reactive stress coping style have elevated antioxidant capabilities and capacities. Overall, our findings suggest that elevated reactivity to neuroendocrine stressors commonly seen in reactive stress coping styles may be mitigated through the glutathione buffering system and other antioxidants.