Stress and Memory Formation Across the Female Lifespan

描述(由申请人提供)：越来越明显的是，男性和女性的差异比我们之前想象的要大得多。它们不仅对压力和环境体验表现出不同的反应，而且还可以做出相反的反应。在老鼠中，暴露在急性应激事件中会增强雄性的联想学习，而显著损害雌性的表现(Wood等人2001年，Wood&Shors 1998年；Shors等人1998年，2002年)。压力对记忆形成的这些相反的影响伴随着对海马体结构中树突棘的存在的类似的相反的影响(Shors等人，2001)。此外，这些相反的压力效应是由两性之间不同的荷尔蒙系统介导的(Wood等人2001年，Beylin&Shors 2002年)。性别差异通常是由性激素的激活和组织效应引起的，这些荷尔蒙在一生中波动，特别是在女性身上。在这一竞争续篇中描述的实验利用了荷尔蒙的波动和情绪性的变化，这些变化发生在非常早期的发育、青春期、产后和更年期。它们被设计成将学习能力和对应激经历的反应的变化与荷尔蒙的变化和海马结构中树突棘的密度联系起来，并将其分离。最后，实验旨在探索学习中的性别差异与海马区生长激素(GH)表达之间的潜在关系，生长激素(GH)是一种优先由学习诱导的基因(Donahue等人，2002年)。技术包括对大鼠的微量眨眼调节、高尔基体染色和光学显微镜分析、实时聚合酶链式反应、原位杂交、放射免疫分析以及糖皮质激素和卵巢激素的手术操作。总体而言，这些研究将确定男性与女性在学习方面的性别差异以及对压力经历的相反反应背后的神经元和激素机制。由于精神障碍经常在这些生活变化中出现或加剧，这些研究将深入了解精神疾病的性别差异，特别是女性经常经历的那些疾病：创伤后应激障碍(PTSD)、单相、产后和绝经后抑郁，以及阿尔茨海默病。

DESCRIPTION (provided by applicant): It has become increasingly clear that males and females differ even more dramatically than we previously thought. Not only do they exhibit differing responses to stress and environmental experience, but they can also respond in opposite directions. In rats, exposure to an acute stressful event enhances associative learning in males while dramatically impairing performance in females (Wood et al 2001, Wood & Shors 1998; Shors et al., 1998, 2002). These opposite effects of stress on memory formation are accompanied by similarly opposite effects on the presence of dendritic spines in the hippocampal formation (Shors et al 2001). Moreover, these opposite effects of stress are mediated by different hormonal systems between the sexes (Wood et al 2001, Beylin & Shors 2002). Sex differences usually arise from activational and organizational effects of sex hormones which fluctuate across the lifespan, especially in females. The experiments described in this competing continuation capitalize on hormonal fluctuations and changes in emotionality that occur during very early development, puberty, post-partum and menopause. They are designed to associate and dissociate changes in learning ability and responses to stressful experience with changes in hormones and density of dendritic spines in the hippocampal formation. Finally, experiments are designed to explore a potential relationship between sex differences in learning and the expression of growth hormone (GH) in the hippocampus, a gene that is preferentially induced by learning (Donahue et al., 2002). Techniques include trace eyeblink conditioning in the rat, Golgi impregnation and light microscope analysis, real-time polymerase chain reaction, in situ hybridization, radioimmunoassay, and surgical manipulation of glucocorticoids and ovarian hormones. Overall, these studies will identity the neuronal and hormonal mechanisms that underlie sex differences in learning and opposite responses to stressful experience in males versus females. Because mental disorders often emerge or are exacerbated during these life changes, the studies will provide insight into sex differences in mental illness, especially those experienced so frequently by women: post-traumatic stress disorder (PTSD), unipolar, post-partum and post-menopausal depression, as well as Alzheimer's disease.