权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

PROJECT 1: VASCULAR AND CELLULAR PATHOLOGY IN DEPRESSION

项目 1：抑郁症中的血管和细胞病理学

基本信息

批准号：
8167932
负责人：
GRAZYNA RAJKOWSKA
金额：
$ 23.4万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8167932
关键词：
Aftercare Age Animals Antidepressive Agents Autopsy Blood Vessels Brain-Derived Neurotrophic Factor Cardiovascular Diseases Cell Count Clinical Research Computer Retrieval of Information on Scientific Projects Database Data Depressed mood Depressive disorder Down-Regulation Electroconvulsive Shock Fibroblast Growth Factor Funding Gene Expression Genes Grant Growth Factor Impairment Individual Institution Lead Link Major Depressive Disorder Mental Depression Microscopic Molecular Molecular Target Monkeys Morphology Neuroglia Neurons Pathology Patients Pharmaceutical Preparations Prefrontal Cortex Reporting Research Research Personnel Resources Risk Factors Rodent Source Stress United States National Institutes of Health Vascular Diseases brain tissue cellular pathology density design inflammatory marker neuroimaging neurotrophic factor novel white matter

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Depression and cardiovascular disease are often comorbid. Clinical studies report impairment of endothelial functions and increased inflammatory markers (risk factor for cardiovascular disease) in depressed patients. Moreover, structural neuroimaging studies demonstrate that depressed patients have more blood vessel pathology in the frontal white matter than age-matched non-depressed controls. However, no studies of vascular morphology and related growth factors at the microscopic and molecular level have been conducted in depression to date. Our preliminary data on microscopic analysis of vessel number and morphology in postmortem brain tissue reveal significant increases in the density of abnormal vessels in the prefrontal cortex (PFC) in depression. These vascular changes were observed in the same subjects that were used in our previous cell counting studies on reductions in the density of neurons and glial cells. Moreover, our recent gene expression studies in these depressed subjects reveal downregulation of genes for fibroblast growth factor (FGF) and brain-derived neurotrophic factor (BDNF), and rodent studies indicate that these factors are reduced in stressed animals and elevated after treatment with electroconvulsive shock or antidepressants. Thus, we hypothesize that in depression there are alterations in vascular morphology that are associated with deficits in angiogenic and neurotrophic factors as well as pathology of neurons and glial cells in the PFC. We further hypothesize that these changes are due to the depressive disorder itself and not due to treatment with antidepressant medication, therefore they will not be observed in the PFC of monkeys treated with antidepressants. This proposal will be the first quantitative microscopic study of cortical vasculature in major depression. It will likely reveal a link between dysfunctional genes and the expression of angiogenic and neurotrophic factors and the pathology of blood vessels, neurons and glial cells in the prefrontal cortex of depressed individuals. This may reveal novel cellular and molecular targets of antidepressant action and possibly lead to the design of more effective medications for depressed patients with vascular disease.

这个子项目是众多研究子项目之一