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。他们不仅对压力和环境经验表现出不同的反应，而且他们也可以以相反的方向做出反应。在大鼠中，暴露于急性应激事件可以增强雄性的联想学习能力，同时显著削弱雌性的表现（Wood et al. 2001, Wood & Shors 1998; Shors et al. 1998, 2002）。压力对记忆形成的这些相反影响，伴随着对海马体形成中树突棘存在的类似相反影响（Shors et al 2001）。此外，压力的这些相反影响是由两性之间不同的激素系统介导的（Wood et al . 2001; Beylin & Shors 2002）。性别差异通常是由性激素的激活和组织效应引起的，性激素在整个生命周期中波动，尤其是在女性中。在这篇竞争性续文中描述的实验利用了发生在早期发育、青春期、产后和更年期的荷尔蒙波动和情绪变化。它们的目的是将学习能力的变化和对压力经历的反应与海马结构中激素和树突棘密度的变化联系起来。最后，实验旨在探索学习中的性别差异与海马中生长激素（GH）表达之间的潜在关系，生长激素是学习优先诱导的基因（Donahue et al., 2002）。技术包括大鼠的微量眨眼调节，高尔基浸透和光镜分析，实时聚合酶链反应，原位杂交，放射免疫测定，以及糖皮质激素和卵巢激素的手术操作。总的来说，这些研究将确定神经元和激素机制，这些机制是男女在学习和对压力经历的相反反应方面的性别差异的基础。由于精神疾病经常在这些生活变化中出现或加剧，因此这些研究将深入了解精神疾病的性别差异，特别是那些女性经常经历的疾病：创伤后应激障碍（PTSD）、单极症、产后和绝经后抑郁症，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.