In this chapter, we will review changes in structural plasticity of the adult hippocampus during stress and exposure to glucocorticoids (GCs). We further discuss the protective and normalizing role of glucocorticoid receptor (GR) antagonist treatment under these conditions and its implications for disorders such as depression and diabetes mellitus.
6.1 The Stress Response
Stress represents an old, yet essential alarm system for an organism. Whenever a discrepancy occurs between an organism's expectations and the reality it encounters, stress systems are activated; particularly when it involves a threat to, or disturbance of its homeostasis, well being, or health. Loss of control, or unpredictability when faced with predator threat in animals, or psychosocial demands in humans, can all produce stress signals. The same holds true for perturbations of a more physical or biological nature, such as energy crises, injury, or inflammation. Upon exposure to a stressor, various sensory and cognitive signals converge to activate a stress response that triggers several adaptive processes in the body and brain which aim to promote restoration of homeostasis.
In mammals, Selye [1] noted that the effect of stressors develops in a stereotypic manner. The first phase largely involves activation of the sympathoadrenal system through the rapid release of epinephrine and norepinephrine from the adrenal medulla; these hormones elevate basal metabolic rate and increase blood flow to vital organs like the heart and muscles. At a later stage, the limbic hypothalamo-pituitary-adrenal (HPA) system is activated as well, a classic neuroendocrine circuit in which limbic and hypothalamic brain structures integrate emotional, cognitive, neuroendocrine, and autonomic inputs, that together determine the magnitude and duration of the organism's behavioral, neural, and hormonal response to a stressor.