Early-life challenges influence adult stress responses

应激事件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。我们的研究主要集中在识别某些生物变化在应对压力源时产生的过程，以及减轻或加剧压力源相关结果的因素（反映脆弱性和弹性因素）。在影响对压力源的反应的许多因素中，早期生活中的不良经历导致神经元和内分泌过程对后来的压力源（致敏或脱敏）的反应更多（或在某些情况下更少），从而可能影响成年期的行为结果。除了在出生后最初几天遇到的压力源的不良影响持续存在外，似乎青少年时期（出生后28-35天）对压力源的影响也非常敏感。拟议的研究将评估心理压力源（反复的社会干扰）和系统压力源（如免疫损伤）对成年后遇到的压力源的行为和神经化学反应的影响。免疫应激源通常会导致与心理应激源引起的生物和行为结果相似的结果，这两种应激源可能具有协同效应或叠加效应。因此，我们认为大脑将免疫激活解释为一种压力源，并可能产生类似于传统压力源引发的反应。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化，从而在成年后的应激源经历中产生夸大的神经化学反应。这些发现暗示了压力事件如何影响大脑功能，以及早期事件如何改变可能具有终身影响的神经发育轨迹。

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.