Early-life challenges influence adult stress responses

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Stressful events provoke marked neuroendocrine, neurochemical and immunological changes, which have been implicated in behavioral disturbances and physical illnesses. Our research has focused on the identification of the processes by which certain biological changes come about in response to stressors, and the factors that that attenuate or exacerbate stressor related outcomes (reflecting vulnerability and resilience factors). Of the many factors that influence the responses to stressors, early life adverse experiences result in neuronal and endocrine processes becoming more (or less in some instances) responsive to later stressors (sensitization or desensitization) and might thus affect behavioral outcomes during adulthood. In addition to protracted adverse effects of stressors encountered in the first few postnatal days, it seems that the juvenile period (postnatal days 28-35) are also highly sensitive to stressor effects. The proposed studies will assess the influence of a psychological stressor (repeated social disturbance) and systemic stressors (e.g., immunological insults) on behavioral and neurochemical responses to stressors subsequently encountered in adulthood. Immune stressors ordinarily lead to biological and behavioral outcomes reminiscent of those elicited by psychological stressors, and the two types of stressors might have synergistic or additive effects. Thus, we suggested that the brain interprets immune activation as a stressor, and might have repercussions akin to those elicited by traditional stressors. In the proposed studies we will assess whether immunogenic challenges and traditional stressors result in the sensitization of neurochemical processes so that upon later stressor experiences in adulthood an exaggerated neurochemical response would ensue. Such findings have implications for how stressful events affect brain functioning, and how early events may alter the trajectory of neural development that may have life-long repercussions.