Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Haifa, Israel.
Neuroendocrinology. 2012;95(1):56-64. doi: 10.1159/000331393. Epub 2012 Feb 22.
Human studies suggest that childhood trauma predisposes individuals to develop stress-related disorders such as depression and post-traumatic stress disorder (PTSD). Recent years have witnessed growing interest in effectively modeling in animals the long-term effects of childhood emotional trauma on stress responses in adulthood. Most studies concerned with the impact of early-life stress on subsequent stress responses in adulthood in rodents have focused on the post-natal pre-weaning period. However, psychiatric studies often refer to human childhood rather than infancy when investigating the patients' traumatic history of stress-related psychopathologies. In accordance with that, we have examined the consequences of stress exposure at a later early-life period, the post-weaning, pre-puberty (juvenile) period, which holds greater resemblance to human childhood. This review summarizes a series of studies examining the impact of exposure of rats to stressors during 'juvenility' ('juvenile stress') on the ability of these animals to cope with stress later in life. Exposure to relatively brief but significant stress experience during juvenility was found to impair the ability of animals to cope with stressful challenges in adulthood. These behavioral manifestations were associated with lasting alterations in limbic system brain regions of neuromodulatory pathways, such as alterations in the expression of cell adhesion molecules, GABAergic system functioning and alterations in levels of circulating corticosterone. Importantly, these studies have also demonstrated considerable individual and sex differences, which call for the development of adequate analysis approaches. The juvenile stress model combined with characterization of individual profiles is presented as a useful model to study in rodents different facets of stress-related disorders and neural mechanisms of vulnerability and resilience to stress.
人类研究表明，童年创伤使个体易患与应激相关的障碍，如抑郁症和创伤后应激障碍（PTSD）。近年来，人们越来越关注在动物中有效地模拟童年情绪创伤对成年期应激反应的长期影响。大多数研究都集中在幼年期后生活压力对成年期后续应激反应的影响上，主要集中在产后断奶前时期。然而，精神科研究在调查与应激相关的精神病理学的患者创伤史时，通常指的是人类的童年，而不是婴儿期。因此，我们研究了生命早期后期，即断奶后、青春期前（青少年）时期暴露于应激的后果，这更类似于人类的童年。这篇综述总结了一系列研究，这些研究检查了在“青少年期”（“青少年应激”）期间使大鼠暴露于应激源对这些动物日后应对压力的能力的影响。研究发现，青少年期短暂但显著的应激经历会损害动物在成年期应对压力挑战的能力。这些行为表现与边缘系统脑区神经调节通路的持久改变有关，例如细胞黏附分子表达的改变、GABA 能系统功能的改变以及循环皮质酮水平的改变。重要的是，这些研究还表明存在相当大的个体和性别差异，这需要开发适当的分析方法。青少年应激模型结合个体特征的描述被提出作为一种有用的模型，用于研究啮齿动物应激相关障碍的不同方面以及对压力的脆弱性和弹性的神经机制。
