Early-life challenges influence adult stress responses

应激事件会引起显著的神经内分泌、神经化学和免疫变化，这些变化与行为障碍和身体疾病有关。我们的研究集中于确定某些生物变化响应应激源的过程，以及减弱或加剧应激源相关结果的因素(反映脆弱性和弹性因素)。在许多影响应激源反应的因素中，早期的不良生活经历会导致神经元和内分泌过程对后来的应激源(敏化或脱敏)的反应变得更多(在某些情况下是更少的)，从而可能影响成年后的行为结果。除了出生后最初几天遇到的压力源的长期不利影响外，似乎青少年时期(出生后28-35天)也对压力源的影响高度敏感。拟议的研究将评估心理应激源(反复的社会干扰)和全身应激源(例如，免疫侮辱)对成年后随后遇到的应激源的行为和神经化学反应的影响。免疫应激源通常会导致生物和行为结果，让人想起那些由心理应激源引起的结果，这两种类型的应激源可能具有协同或相加的效应。因此，我们认为大脑将免疫激活解释为应激源，并可能产生类似于传统应激源引发的反应。在拟议的研究中，我们将评估免疫原性挑战和传统应激源是否会导致神经化学过程的敏感化，以便在成年后经历应激源时，会接踵而至的是夸大的神经化学反应。这些发现对应激事件如何影响大脑功能，以及早期事件如何改变神经发育的轨迹可能产生终身影响都有一定的影响。

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.