Novelty stressor induces differential brain 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. To what extent the relationship between neuroendocrine and oxidative stress is modulated by stress coping styles remain unclear. We subjected proactive and reactive zebrafish to an acute novelty stressor (i.e. neuroendocrine stressor), and 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). Fish exposed to the novelty stressor had significantly higher total glutathione, trend for higher ORAC, DNA damage, and glutathione ratio, and trend for lower SOD levels than controls. Those with a reactive stress coping style exhibited significantly higher levels of SOD and glutathione ratio, and a trend for higher ORAC compared to proactive. Principal component analysis showed that reactive individuals that experienced the novelty stressor had significantly higher composite antioxidant scores than proactive. Our data show that exposure to a novelty stressor results in changes to antioxidant and oxidative stress levels in the brain that differs by stress coping style. Reactive individuals showed elevated antioxidant capacity. 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.