Environmental influences that alter the stress circuitry.
Environmental influences that alter the stress circuitry.
复制标题
改变压力电路的环境影响。
DOI：
10.1055/s-0032-1316326
复制
发表时间：
2012
期刊：
影响因子：
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通讯作者：
Tamashiro,KLK
中科院分区：
文献类型：
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作者：
Ismail,N;Sotomayor-Zarate,R;Bale,TL;Blaustein,JD;Gysling,K;Tamashiro,KLK
增加神经发育和社会行为障碍的发病率，如精神分裂症和自闭症谱系障碍[3-5]。诸如压力或母体饮食等因素导致后代疾病风险增加的机制尚不清楚，但可能是由于母体环境，胎盘变化和胚胎表观遗传编程之间的复杂相互作用。此外，目前还不清楚后代性别如何影响对母体环境变化的表观遗传反应[6]。在雄性小鼠中，妊娠早期似乎是最容易受到母体压力编程影响的时期[7]。更具体地说，产前暴露于压力会通过某些行为指标（如成年后的压力反应）使男性后代的男性化障碍来破坏既定的性别差异[8]。人类研究表明，产前暴露于母亲抑郁或焦虑的婴儿显示出更高水平的糖皮质激素甲基化，这与应对轻度应激源时皮质醇释放增加有关[9]。由于编程表观遗传变化可以传递给后代，因此产前压力可能会使后代后代易于患上这种神经发育障碍。支持这种可能性的是使用早期生活压力模型的动物研究。例如，暴露于长期和不可预测的母亲分离的雄性小鼠在成年后表现出抑郁样行为和对厌恶环境的行为反应改变。暴露于母体分离的小鼠在几个候选基因的启动子区也显示出改变的DNA甲基化谱。有趣的是，经历母体分离的雄性小鼠的后代显示出相当的行为改变和DNA甲基化的变化[10]。这些发现不仅强调了早期生活压力对HIV的负面影响-在早期发育中，有关键时期，如产前，围产期和青春期，在此期间，化学，生物和物理损伤（即营养限制，母体压力等）。对后代的生理、代谢和健康产生永久性的改变[1]。虽然大多数人能够科普压力事件，并且在压力恢复之前仅显示出短暂的压力反应和增强的生理活动，但在这些关键时期暴露于压力事件可能导致相当数量的人发展长期的精神病理学状况[2]。遗传和环境因素之间复杂的相互作用可能是这种异质性的起源。这些会议记录是基于美国-南美神经内分泌学研讨会的研讨会。会议的基础是在发展的关键时期暴露于压力因素的各种影响。因此，在这些程序中，我们讨论了在发育的关键时期暴露于压力源对心理健康，性别分化，行为，代谢和大脑中基因表达的影响。这些程序并不意味着是对文献的全面审查。它只是为了汇集讲习班期间提出的各种影响。
increase the incidence of neurodevelopmental and social behavior disorders, like schizophrenia and autism spectrum disorders [3–5]. The mechanisms through which factors such as stress or maternal diet contribute to increased offspring disease risk remain unclear, but are likely due to a complex intereaction between the maternal environment, placental changes, and epigenetic programming of the embryo. Moreover, it is unclear how offspring sex may influence the epigenetic response to a changing maternal environment [6]. The early gestational period appears to be the most vulnerable period to the programming effects of maternal stress in male mice [7]. More specifically, exposure to stress prenatally disrupts established sex differences by dysmasculinizing male offsprings on certain behavioral measures, such as stress responsivity in adulthood [8]. Human studies have shown that infants exposed prenatally to maternal depression or anxiety display higher levels of glucocorticoid methylation, which is associated with increased cortisol release in response to a mild stressor [9]. Since programming epigenetic changes can be transmitted to subsequent generations, it is possible that exposure to prenatal stress may predispose offspring of future generations to such neurodevelopmental disorders. Support for this possibility comes from animal research using models of early life stress. For instance, male mice exposed to chronic and unpredictable maternal separation display depression-like behavior and altered behavioral response to aversive environments in adulthood. Mice exposed to maternal separation also display altered DNA methylation profile in the promoter region of several candidate genes. Interestingly, the offspring of male mice subjected to maternal separation show comparable behavioral alterations and changes in DNA methylation [10]. These findings not only emphasize the negative impact of early life stress on behav-In early development, there are critical periods, such as prenatal, perinatal, and pubertal periods, during which chemical, biological, and physical insults (ie, nutritional restriction, maternal stress, etc.) exert permanent alterations on physiology, metabolism, and health of offspring [1]. Although most people are able to cope with stressful events and only display a brief stress response with heightened physiological activity before stress recovery, exposure to stressful events during these critical periods can lead to the development of long-term psychopathological conditions in a significant number of people [2]. A complex interplay between genetic and environmental factors is probably at the origin of this heterogeneity. These proceedings are based on a workshop session at the US-South America Workshop in Neuroendocrinology. The session was based on the diverse effects of exposure to stressors during critical periods of development. Therefore, in these proceedings, we discuss the effects of exposure to a stressor during critical periods of development on mental health, sexual differentiation, behavior, metabolism, and gene expression in the brain. These proceedings are not meant to be a comprehensive review of the literature. It is simply meant to bring together the diverse effects presented during the workshop.