Meeting Abstract

65.7  Monday, Jan. 6 11:30  Protective and Damaging Effects of Mediators of Stress and Adaptation MCEWEN, B.S. ; The Rockefeller University mcewen@rockefeller.edu

An ever-changing environment requires an organism to adapt via a process called “allostasis” using the neuroendocrine, autonomic, immune and metabolic systems that interact with each other and function in a non-linear manner. The long term consequence of allostasis is cumulative changes in brain and body, leading to adaptation to a new challenge, often referred to as a stressor. Referred to as “allostatic load and overload”, such structural and functional changes are often used in the natural world for successful adaptation and survival of an individual or species. Yet, in humans and also in animals in captivity, allostatic overload in the form of cardiovascular disease, diabetes, depression and other disorders represent the cost of a sedentary lifestyle where caloric intake exceeds utilization, but also may include the consequences of poverty,crowding, social isolation and other forms of deprivation and adversity. The brain is the central organ of stress and adaptation to stressors and it is a plastic and vulnerable organ throughout the life course. Among the many interacting mediators that affect brain and body function, glucocorticoids stand out because they are involved in so many different processes and via multiple cellular and molecular mechanisms, in which epigenetic mechanisms are prominent. Their actions follow a U-shaped (hormetic) dose response relationships and they have both trophic and protective effects at one end and damage-facilitating effects at the other. This will be discussed in relation to the role of the hippocampus, amygdala and prefrontal cortex in effects of acute and chronic stress in animal models and in humans. Implications for therapy of stress-related disorders will be discussed.