Stress and related effects on mitochondrial performance and function

Increasing evidence suggests that exposure to stress is involved in cellular survival and might contribute to neuronal cell loss occurring during aging and in many stress-related mental disorders. Mitochondria, key regulators of cell survival and death, play an important role in cytoprotection and neural plasticity. One of the most important stress hormones in humans is the glucocorticoid cortisol. Glucocorticoids play a major role in the response of the brain to stress. It has been shown that low doses of glucocorticoids have trophic actions on neuronal survival, while sustained elevations of glucocorticoids act detrimental on neuronal survival. Recent reports show that these effects are partly mediated by the glucocorticoid receptors which might translocate into mitochondria and modulate mitochondrial gene expression. To better understand the impact of glucocorticoids on neuronal mitochondria it was sought to determine their effects on various aspects of mitochondrial function e.g. the mitochondrial membrane potential, ATP production and ROS level. For this, human neuroblastoma cells were treated for different time periods with both physiologic and pathophysiologic levels of cortisol. It was found that cortisol altered neuronal mitochondrial function. Not only the cortisol level was deciding but also the duration period of exposure to the stress factor was crucial of how the glucocorticoid modified the mitochondrial function.