Hormones and Brain Protection

描述（由申请人提供）：参与鸟鸣控制的大脑区域的季节性回归提供了一个引人注目和独特的机会来研究与自然发生的类固醇激素变化相关的神经元退化和保护的调节机制，以及神经保护对习得的感觉运动行为的功能后果。本提案的目的是解决成人大脑中激素作为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（Aims 1-4），激酶级联在介导激素的跨突触神经保护作用中的作用（Aim 3），以及类固醇是否能够以独立于激素受体的方式发挥神经保护作用（Aim 2）。鸟鸣系统是研究神经保护的激素机制的典范。这是一个定义明确、易于处理的神经回路，显示出激素调节的神经元回归和保护的极端季节性模式。这些神经退化和保护过程与繁殖相关的激素周期一起发生，因此无需侵入性操作即可在体内研究。这项研究将通过以下方式推进该领域的发展：1)提供首个证据证明歌曲系统

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.