MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

基本信息

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
项目类别：
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

项目摘要

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）的基础水平和应激水平对认知的不同影响可以通过两种类型的GC受体的存在来解释，即对GC具有高亲和力的I型盐皮质激素受体（MR）并介导 GC 分泌对认知的有益影响。相比之下，II 型糖皮质激素受体对 GC 的亲和力较低，并且仅在高 GC 浓度下才被激活，这可能会损害空间辨别力和突触可塑性。本研究计划的目的是构建表达 MR 的载体，并表征过度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 过度表达对压力引起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得将外源DNA引入并过度表达至中枢神经系统成为可能。在本研究中，我们将使用过表达 MR 的 HSV 扩增子来研究其对海马依赖性认知中应激引起的损伤的神经保护潜力及其增强认知和突触可塑性的潜力。