Richardson Heather N, Zorrilla Eric P, Mandyam Chitra D, Rivier Catherine L
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Endocrinology. 2006 May;147(5):2506-17. doi: 10.1210/en.2005-1054. Epub 2006 Feb 2.
Early life experiences can shape brain function and behavior in adulthood. The present study sought to elucidate the effects of repetitive, predictable vs. varied, unpredictable prenatal stress on sexually dichotomous neuroendocrine and anxiety-related behavioral responses in adult offspring. Rat dams were exposed repeatedly during the last week of pregnancy to no stress, only restraint stress [prenatal stress (PS)-restraint], or a randomized sequence of varied stressors (PS-random), and several behavioral and endocrine measures were assessed in adult male and female offspring. Repeated exposure to the same stressor (restraint) generated the most robust changes, including increased anxiety-related behaviors (both passive, measured on the elevated plus maze, and active, measured using defensive burying tests), a delayed and prolonged hypothalamic-pituitary-adrenal (HPA) axis response to stress in female offspring. Conversely, PS-restraint males showed no changes in anxiety-like behavior and had elevated basal ACTH and a blunted HPA response to stress; consistent with attenuated HPA responsivity was an increase in glucocorticoid receptor immunoreactivity in the hippocampus, suggesting increased negative feedback on the HPA axis in these animals. Prenatal exposure to a varied, unpredictable pattern of stressors did not have as much effect on HPA function, with most neuroendocrine measures residing intermediate to PS-restraint and control animals within each sex. Gonadal steroids were altered independent of the type of prenatal stress, but changes were measurable only in males (lower testosterone). The present data exemplify the differential sensitivity of the developing nervous and endocrine systems to stress, depending on not only gender but also the nature of the stressful experience endured by the mother during pregnancy.
早期生活经历能够塑造成年期的大脑功能和行为。本研究旨在阐明重复性、可预测的与多变、不可预测的产前应激对成年后代性别二分的神经内分泌及焦虑相关行为反应的影响。在妊娠最后一周，将孕鼠反复暴露于无应激、仅束缚应激[产前应激（PS）-束缚]或多种应激源的随机序列（PS-随机）环境中，并对成年雄性和雌性后代的多种行为和内分泌指标进行评估。反复暴露于相同应激源（束缚）产生了最显著的变化，包括焦虑相关行为增加（被动方面，通过高架十字迷宫测量；主动方面，通过防御性埋埋测试测量），雌性后代下丘脑-垂体-肾上腺（HPA）轴对应激的反应延迟且延长。相反，PS-束缚组雄性在焦虑样行为方面没有变化，基础促肾上腺皮质激素水平升高，HPA对应激的反应减弱；与HPA反应性减弱一致的是海马体中糖皮质激素受体免疫反应性增加，表明这些动物对HPA轴的负反馈增加。产前暴露于多变、不可预测的应激源模式对HPA功能的影响较小，大多数神经内分泌指标在各性别中处于PS-束缚组和对照组动物之间。性腺类固醇的改变与产前应激类型无关，但仅在雄性中可检测到变化（睾酮水平降低）。本研究数据例证了发育中的神经和内分泌系统对应激的敏感性差异，这不仅取决于性别，还取决于母亲在孕期所经历应激的性质。
