Rapid steroidogenesis in the brain.

描述（由申请人提供）：重要的行为和生理变化发生在几分钟的时间尺度上，但这些快速变化背后的神经内分泌机制尚未得到很好的理解。类固醇激素代表了这种快速神经和行为效应的一组候选分子。虽然类固醇激素是强大而普遍的神经调节剂，但人们对大脑（神经类固醇）内类固醇水平如何在快速时间段内进行调节知之甚少。缩小理解这一整类神经调质的差距，将有助于深入了解神经递质系统和神经类固醇如何在每分钟的基础上相互作用。初步的临床研究表明，神经类固醇的病理生理学参与的疾病，如产后抑郁症，妊娠疲劳，癫痫。因此，更好地了解神经类固醇水平如何随时间变化可能会提高我们对社会行为，心理健康和疾病的理解。在这个建议中，表征类固醇生成酶在大脑中的活性，以及在体内测量大脑类固醇水平，是理解类固醇的神经调节作用和类固醇转换的功能的关键和补充的方法。该提案旨在阐明大脑类固醇水平的快速变化如何有助于大脑功能和社会行为的变化。在斑胸草雀模型中，拟议的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和类固醇生成酶活性的变化相关。拟议中的实验还将研究在急性应激期间大脑类固醇水平和类固醇生成酶活性的快速变化。人类和鸣禽都表现出显着的类固醇从非性腺来源，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。

DESCRIPTION (provided by applicant): 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.