MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 7156911
• 负责人: Deveroux Ferguson
• 金额: $ 2.52万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156911
• 关键词: Adrenal Glands; Affinity; Antibodies; Antidepressive Agents; Behavioral; Binding; Biological Assay; Chemosensitization; Chronic; Cognition; Condition; Corticosterone; DNA; Data; Depressed mood; Disruption; Environment; Exposure to; Facility Construction Funding Category; Fellowship; Fellowship Program; Genbank; Glucocorticoid Receptor; Glucocorticoids; Green Fluorescent Proteins; HSV vector; Hippocampus (Brain); Immunoblotting; Impairment; In Vitro; Individual; Injection of therapeutic agent; Label; Learning; Long-Term Depression; Long-Term Potentiation; Mediating; Memory; Memory impairment; Mineralocorticoid Receptor; Minority; Names; Neuraxis; Neurons; Plasmids; Polymerase Chain Reaction; Property; Protein Overexpression; Rattus; Receptor Activation; Receptor Gene; Receptor Signaling; Relative (related person); Research Proposals; Rest; Simplexvirus; Site; Slice; Space Perception; Steroid Receptors; Stress; Synaptic plasticity; System; Testing; Time; Tissues; Transgenes; biological adaptation to stress; cognitive function; day; dentate gyrus; in vivo; morris water maze; neuronal excitability; neurotransmission; object recognition; pre-doctoral; promoter; protective effect; protein expression; research study; vector

DESCRIPTION (provided by applicant): The differential effects of basal and stress levels of glucocorticoids (GCs) on cognition can be explained by the presence of two types of GC receptors, the type I mineralocorticoid receptor (MR) which has a high affinity for GCs and mediates the beneficial effects of GC secretion on cognition. In contrast, the type II glucocorticoid receptor has a low affinity for GCs and is only activated at a high GC concentration, which is implicated in impairing spatial discrimination and synaptic plasticity. This research proposal aims are to construct a vector expressing the MR and characterize the effects of overexpression on basal cognitive functions and synaptic plasticity. In addition, we will assess the neuroprotective potential of MR overexpression against stress-induced memory impairments and synaptic plasticity. A modified herpes simplex virus amplicon system has made it feasible to introduce and overexpress foreign DNA into the central nervous system. In the present study we will use a HSV amplicon overexpressing MR to investigate its neuroprotective potential against stress-induced impairments in hippocampal-dependent cognition and its potential to enhance cognition and synaptic plasticity.

描述（由申请人提供）：糖皮质激素（GC）的基础和应激水平对认知的不同作用可以通过两种类型GC受体的存在来解释，I型盐皮质激素受体（MR）对GC具有高亲和力，并介导GC分泌对认知的有益作用。相反，II型糖皮质激素受体对GC具有低亲和力，并且仅在高GC浓度下被激活，这与损害空间辨别和突触可塑性有关。本研究的目的是构建表达MR的载体，并表征过表达对基础认知功能和突触可塑性的影响。此外，我们将评估MR过表达对应激诱导的记忆障碍和突触可塑性的神经保护潜力。改良的单纯疱疹病毒扩增子系统使外源DNA导入中枢神经系统并过表达成为可能。在本研究中，我们将使用一个HSV扩增子过表达MR研究其神经保护潜力对应激诱导的障碍，在海马依赖的认知和它的潜力，以提高认知和突触可塑性。