Amygdala GR Function in Stress Activation and Promotion

描述（由申请人提供）：抑郁症，一种破坏性的精神障碍，估计每年影响1800万人。与抑郁相关的焦虑和记忆变化与下丘脑-垂体-肾上腺（HPA）轴（内分泌应激反应）的失调有关。在慢性应激状态下，HPA轴和行为变化可以是积极的（即增加HPA驱动和行为）或消极的（即减少HPA驱动）。据推测，压力对焦虑和记忆的各种影响至少可以部分地由糖皮质激素受体（GR）活性的改变来解释。与这一假设一致，药理学和遗传学研究的证据表明，不同大脑区域中不同数量的GR活性能够产生焦虑和记忆方面的不同变化。具体而言，海马和下丘脑的GR参与减少HPA轴驱动，而杏仁核的GR被认为参与增加驱动和焦虑。为了确定杏仁核GR在抑郁症相关变化和HPA轴调节中的作用，目前的基因治疗和基因敲除技术将用于制造杏仁核GR破坏的小鼠。

DESCRIPTION (provided by applicant): Depression, a destructive psychiatric disorder, is estimated to affect 18 million people per year. Anxiety and memory changes associated with depression have been connected to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the endocrine stress response. HPA axis and behavioral changes can be either positive (i.e., increasing HPA drive and behavior) or negative (i.e., decreasing drive) in a state of chronic stress. It has been postulated that the various effects of stress on anxiety and memory can be at least partially accounted for by the altered activity of glucocorticoid receptors (GR). In accord with this hypothesis, evidence from pharmacological and genetic studies has demonstrated the capacity of differing amounts of GR activity in different brain areas to produce contrasting changes on anxiety and memory. Specifically, GRs in the hippocampus and hypothalamus are involved in decreasing HPA axis drive while GR in the amygdala is thought to be involved in increasing drive and anxiety. To determine the role of amygdalar GR in depression-related changes and HPA axis modulation, current gene therapy and knockout technology will be used to produce mice with amygdalar disruption of GR.