Amygdala GR Function in Stress Activation and Promotion

杏仁核 GR 在应激激活和促进​​中的功能

• 批准号: 7452398
• 负责人: BENEDICT J KOLBER
• 金额: $ 1.45万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-03 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7452398
• 关键词: Accounting; Acute; Adrenal Glands; Affect; American; Amygdaloid structure; Anxiety; Area; Behavior; Behavioral; Biological; Brain; Cell Nucleus; Chronic stress; Cognitive; Condition; Corticosterone; Corticotropin; Cues; Disruption; Economic Burden; Emotional; Endocrine; Evaluation; Family; Feedback; Fright; Genetic; Glucocorticoid Receptor; Glucocorticoids; Grant; Green Fluorescent Proteins; Hippocampus (Brain); Hormones; Hypothalamic structure; In Vitro; Knock-out; LacZ Genes; Learning; Lentivirus Vector; Link; Localized; Major Depressive Disorder; Mediating; Medical Economics; Memory; Mental Depression; Mental disorders; Molecular; Molecular Target; Mus; Nuclear Hormone Receptors; Pathogenesis; Patients; Peptide Receptor; Pituitary Gland; Play; Production; Proteins; Regulation; Reporter; Role; Rosa; Stress; Syndrome; Technology; Thinking; base; biological adaptation to stress; burden of illness; cognitive change; conditioned fear; design; dexamethasone suppression test; driving behavior; experience; gene therapy; hypothalamic-pituitary-adrenal axis; in vivo; member; morris water maze; preference; receptor expression; receptor function; recombinase; response

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.

描述（由申请人提供）：抑郁症是一种破坏性的精神疾病，估计每年影响 1800 万人。与抑郁症相关的焦虑和记忆力改变与下丘脑-垂体-肾上腺（HPA）轴（内分泌应激反应）失调有关。在慢性压力状态下，HPA 轴和行为变化可以是积极的（即增加 HPA 驱动力和行为）或消极的（即减少驱动力）。据推测，压力对焦虑和记忆的各种影响至少可以部分归因于糖皮质激素受体（GR）活性的改变。根据这一假设，药理学和遗传学研究的证据表明，不同大脑区域中不同量的 GR 活动能够对焦虑和记忆产生对比变化。具体来说，海马和下丘脑中的 GR 与 HPA 轴驱动力的降低有关，而杏仁核中的 GR 被认为与驱动力和焦虑的增加有关。为了确定杏仁核 GR 在抑郁相关变化和 HPA 轴调节中的作用，当前的基因治疗和敲除技术将用于产生杏仁核 GR 破坏的小鼠。