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:8360506
- 负责人:
- 金额:$ 20.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-01 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:AftercareAgeAngiogenic FactorAnimalsAntidepressive AgentsAutopsyBlood VesselsBrain-Derived Neurotrophic FactorCardiovascular DiseasesCell CountClinical ResearchDataDepressed moodDepressive disorderDown-RegulationElectroconvulsive ShockFibroblast Growth FactorFundingGene ExpressionGenesGrantGrowth FactorImpairmentIndividualLeadLinkMajor Depressive DisorderMental DepressionMicroscopicMolecularMolecular TargetMonkeysMorphologyNational Center for Research ResourcesNeurogliaNeuronsNeurosciencesPathologyPatientsPharmaceutical PreparationsPrefrontal CortexPrincipal InvestigatorReportingResearchResearch InfrastructureResourcesRisk FactorsRodentSourceStressUnited States National Institutes of HealthVascular Diseasesbrain tissuecellular pathologycellular targetingcostdensitydesigninflammatory markerneuroimagingneurotrophic factornovelwhite 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. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
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.
这个子项目是利用资源的许多研究子项目之一。
由NIH/NCRR资助的中心拨款提供。对子项目的主要支持
子项目的首席调查员可能是由其他来源提供的,
包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能
表示该子项目使用的中心基础设施的估计数量,
不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。
抑郁症和心血管疾病常常是并存的。临床研究报告了抑郁症患者的内皮功能受损和炎症标志物(心血管疾病的风险因素)增加。此外,结构神经成像研究表明,抑郁症患者额叶白质的血管病变比年龄匹配的非抑郁症对照组更多。然而,到目前为止,还没有在微观和分子水平上对抑郁症的血管形态和相关生长因子进行研究。我们对死后脑组织血管数量和形态的显微镜分析的初步数据显示,抑郁症患者前额叶皮质(PFC)异常血管密度显著增加。这些血管变化是在我们之前的细胞计数研究中观察到的,这些对象是关于神经元和神经胶质细胞密度减少的。此外,我们最近对这些抑郁受试者的基因表达研究显示,成纤维细胞生长因子(FGF)和脑源性神经营养因子(BDNF)的基因下调,而啮齿动物研究表明,这些因子在应激动物中减少,在电惊厥或抗抑郁药物治疗后升高。
因此,我们假设抑郁症患者存在血管形态的改变,这些改变与血管生成因子和神经营养因子的缺乏以及前额叶神经元和神经胶质细胞的病理改变有关。我们进一步假设,这些变化是由于抑郁障碍本身,而不是由于抗抑郁药物的治疗,因此它们不会在接受抗抑郁药物治疗的猴子的PFC中观察到。这项建议将是首次对重度抑郁症患者的皮质血管系统进行的定量显微研究。它可能会揭示功能障碍基因与血管生成和神经营养因子的表达以及抑郁症患者前额叶皮质血管、神经元和神经胶质细胞的病理之间的联系。这可能揭示抗抑郁作用的新的细胞和分子靶点,并可能导致为患有血管疾病的抑郁症患者设计更有效的药物。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GRAZYNA RAJKOWSKA其他文献
GRAZYNA RAJKOWSKA的其他文献
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{{ truncateString('GRAZYNA RAJKOWSKA', 18)}}的其他基金
PROJECT 1: VASCULAR AND CELLULAR PATHOLOGY IN DEPRESSION
项目 1:抑郁症中的血管和细胞病理学
- 批准号:
8167932 - 财政年份:2010
- 资助金额:
$ 20.66万 - 项目类别:
Human Post-Mortem Pathology (in-situ Hyb etc.)
人类死后病理学(原位杂交等)
- 批准号:
8118886 - 财政年份:2010
- 资助金额:
$ 20.66万 - 项目类别:
PROJECT 1: VASCULAR AND CELLULAR PATHOLOGY IN DEPRESSION
项目 1:抑郁症中的血管和细胞病理学
- 批准号:
7959829 - 财政年份:2009
- 资助金额:
$ 20.66万 - 项目类别:
PROJECT 1: VASCULAR AND CELLULAR PATHOLOGY IN DEPRESSION
项目 1:抑郁症中的血管和细胞病理学
- 批准号:
7720504 - 财政年份:2008
- 资助金额:
$ 20.66万 - 项目类别:
Human Post-Mortem Pathology (in-situ Hyb etc.)
人类死后病理学(原位杂交等)
- 批准号:
7478381 - 财政年份:2007
- 资助金额:
$ 20.66万 - 项目类别:
Human Post-Mortem Pathology (in-situ Hyb etc.)
人类死后病理学(原位杂交等)
- 批准号:
7167302 - 财政年份:2006
- 资助金额:
$ 20.66万 - 项目类别:
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