Rapid steroidogenesis in the brain.

重要的行为和生理变化发生在几分钟的时间尺度上，但神经内分泌 这些快速变化背后的机制尚未得到很好的理解。类固醇激素代表一种 一组候选分子，用于这种快速的神经和行为效应。虽然类固醇激素是 强大而普遍的神经调质，很少有人知道大脑中的类固醇水平如何 （神经类固醇）在快速的时间段内被调节。缩小理解这门课的差距 神经调质的研究将深入了解神经递质系统和神经类固醇如何相互作用， 一分钟一分钟的。初步临床研究表明，神经类固醇 病理生理学涉及诸如产后抑郁症、妊娠疲劳和 癫痫因此，更好地了解神经类固醇水平随时间的变化可能会改善我们的神经功能。 了解社会行为、心理健康和疾病。在这项提案中， 脑中类固醇生成酶以及脑类固醇水平的体内测量是关键的， 了解类固醇的神经调节作用和类固醇的功能的补充方法， 类固醇通过大脑转化这项提案旨在阐明大脑类固醇水平的快速变化 有助于改变大脑功能和社会行为。在斑胸草雀模型中， 实验将评估唱歌行为如何与体内大脑类固醇水平的快速变化有关， 和类固醇生成酶活性的变化。拟议中的实验还将检查快速变化 在急性应激期间脑类固醇水平和类固醇生成酶活性。人类和鸣禽 表现出显著的非性腺来源的类固醇合成，包括大脑，所以这些实验 提供了一个机会，以提高我们的基本神经类固醇机制的理解。

Important behavioral and physiological changes occur on a timescale of minutes, yet the neuroendocrine mechanisms that underlie these fast changes are not well understood. Steroid hormones represent one group of candidate molecules for such rapid neural and behavioral effects. Although steroid hormones are powerful and pervasive neuromodulators, little is known about how steroid levels within the brain (neurosteroids) are regulated over rapid time periods. Narrowing the gap in understanding this entire class of neuromodulators will provide insight into how neurotransmitter systems and neurosteroids interact on a minute-by-minute basis. Preliminary clinical investigations have indicated that neurosteroid pathophysiologies are involved in disorders such as postpartum depression, pregnancy fatigue, and epilepsy. Thus, a greater appreciation of how neurosteroid levels change overtime may improve our understanding of social behavior, mental health and disease. In this proposal, characterizing the activity of steroidogenic enzymes in the brain, as well as in vivo measurement of brain steroid levels, are critical and complementary approaches toward understanding the neuromodulatory role of steroids and the function of steroid conversion by the brain. This proposal seeks to clarify how rapid changes in brain steroid levels contribute to changes in brain function and social behavior. In the zebra finch model, the proposed experiments will assess how singing behavior is related to rapid changes in both brain steroid levels in vivo and changes in steroidogenic enzyme activity. The proposed experiments will also examine rapid changes in brain steroid levels and steroidogenic enzyme activity during acute stress. Both humans and songbirds exhibit significant steroidogenesis from non-gonadal origins, including brain, and so these experiments provide an opportunity to improve our understanding of basic neurosteroid mechanisms.