Hormones and Brain Protection

激素和大脑保护

• 批准号: 8604176
• 负责人: ELIOT A BRENOWITZ
• 金额: $ 32.1万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604176
• 关键词: Address; Adult; Aging; Androgen Receptor; Androgens; Apoptotic; Behavior; Biochemistry; Birds; Brain; Brain Injuries; Brain region; Breeding; Cell Nucleus; Cognitive; Complex; Data; Degenerative Disorder; Disease; Electrophysiology (science); Employee Strikes; Endocrinology; Ensure; Estrogen Receptors; Estrogens; Genes; Genetic Transcription; Genomics; Goals; Gonadal Steroid Hormones; Growth; Hormonal; Hormone Receptor; Hormones; Infusion procedures; Intervention; Learning; Measures; Mediating; Mental disorders; Modeling; Molecular; Molecular Biology; Nerve Degeneration; Neurons; Neuroprotective Agents; Outcome; Pattern; Phosphatidylinositols; Phosphotransferases; Physiological; Play; Process; Prosencephalon; Public Health; Receptor Activation; Research; Research Personnel; Role; Route; Signal Pathway; Signal Transduction; Sirolimus; Steroids; Structure; Study models; System; Testing; Testosterone; Therapeutic; Uncertainty; Variant; Vertebral column; Work; bird song; drug of abuse; experience; in vivo; inhibitor/antagonist; innovation; interdisciplinary approach; morphometry; neural circuit; neurogenesis; neuronal cell body; neuronal survival; neurophysiology; neuroprotection; novel; prevent; programs; protective effect; research study; stereotypy; steroid hormone

DESCRIPTION (provided by applicant): Seasonal regression of brain regions involved in the control of birdsong provides a striking and unique opportunity to investigate the mechanisms regulating neuronal degeneration and protection associated with naturally occurring variation in steroid hormones, and the functional consequences of neuroprotection for a learned sensorimotor behavior. The aims in this proposal address fundamental issues of hormones as neuroprotective agents in adult brains. These include the role of indirect genomic signaling pathways in hormonal neuroprotection (Aims 1-4), the role of kinase cascades in mediating transynaptic neuroprotective effects of hormones (Aim 3), and whether steroids can have neuroprotective effects in a manner independent of hormone receptors (Aim 2). The birdsong system excels as a model for studies of hormonal mechanisms of neuroprotection. It is a well-defined and tractable neural circuit that shows extreme seasonal patterns of hormone-regulated neuronal regression and protection. These processes of neural degeneration and protection occur with breeding-related hormonal cycles and thus can be studied in vivo without invasive manipulations. This research will advance the field by 1) providing the first evidence in the song system that kinase cascades are "indirect" genomic contributors to hormonal neuroprotection (Aims 1-4); 2) investigating the mechanisms by which hormones act transynaptically to have neuroprotective effects, and whether kinase cascades mediate this effect (Aim 3); and 3) determining whether the contribution of kinase cascades to the neuroprotective effect of steroids requires hormone receptor activation (Aim 2), an issue of continuing uncertainty.

描述（由申请人提供）：参与控制鸟鸣的大脑区域的季节性回归提供了一个惊人且独特的机会来研究调节与类固醇激素自然发生变化相关的神经元变性和保护的机制，以及神经保护对鸟类的功能影响。学习感觉运动行为。该提案的目的是解决激素作为成人大脑神经保护剂的基本问题。这些包括间接基因组信号通路在激素神经保护中的作用（目标 1-4）、激酶级联在介导激素突触神经保护作用中的作用（目标 3）以及类固醇是否能够以独立于激素受体的方式产生神经保护作用（目标 2）。鸟鸣系统非常适合作为神经保护激素机制研究的模型。它是一个明确且易于处理的神经回路，显示出激素调节的神经元退化和保护的极端季节性模式。这些神经变性和保护过程与繁殖相关的激素周期一起发生，因此可以在体内进行研究，而无需侵入性操作。这项研究将通过以下方式推进该领域的发展：1）在歌曲系统中提供第一个证据： 激酶级联是激素神经保护的“间接”基因组贡献者（目标 1-4）； 2) 研究激素通过突触发挥神经保护作用的机制，以及激酶级联是否介导这种作用（目标 3）； 3) 确定激酶级联对类固醇神经保护作用的贡献是否需要激素受体激活（目标 2），这是一个持续不确定的问题。