THIS GRANT IS A CONTINUATION OF N00014-13-1-0571 Biomarkers and Mechanisms of Resilience vs. Susceptibility to Stress
Abstract
Stress is an intrinsic and increasingly dominant part of life for all human beings, including members of the Navy. It can be defined as a constellation of events that begins with a stimulus (stressor) that is detected by the brain (stress perception) that then activates fight-or-flight-systems in the body (biological stress response). The physiological stress response results in the release of neurotransmitters, hormones, peptides, and other factors into the circulation, or locally within tissues. The major mediators of stress effects are norepinephrine and epinephrine that are released by the sympathetic nervous system, and corticotrophin-releasing hormone, adrenocorticotropin (ACTH), and cortisol that make up the hypothalamic-pituitary-adrenal (HPA)axis. Science has shown that chronic/long term (months-years) stress can have numerous deleterious effects and exacerbate numerous disorders such as depression, heart disease, obesity, cancer, and autoimmune and infectious disease. On the other hand, acute/short term (0.5-2 hours) stress has been shown to have protective beneficial effects. For example, acute stress experienced at the time of immune activation enhances protective immunity during vaccination, surgery, and cancer. It has been proposed that a state of optimal well-being is when chronic stress is minimized or eliminated; acute stress responses are mobilized rapidly and robustly for short durations when threats, challenges, or arousing situations occur; and the resting state equilibrium, characterized by very low levels of stress hormones and related factors between periods of stress, is maximized. In order to maximize the positive effects of stress and minimize the negative effects of stress, it is important to identify, quantify, and understand the biological factors that mediate the effects of stress and serve as objective measures (i.e. biomarkers) of stress. The proposed research project aims to identify the markers and mediators of resistance to the effects of chronic stress (i.e. resilience), susceptibility to the effects of chronic stress, and recovery from chronic stress. An outbred mouse model for long-term stress that mimics the repeated pattern of stress that most humans, including Navy personnel, experience will be established. Restraint will be the model stressor. Biomarkers of blood and skin will be emphasized because these are readily accessible compartments in humans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 03, 2016
- Source ID
- N000141612096
Entities
People
- Firdaus Dhabhar
Organizations
- Office of Naval Research
- Stanford University
- United States Navy