Mechanisms of NAD Metabolism and Chronic Inflammation in HIV-1 Transgenic Rat Models
HIV-1转基因大鼠模型中NAD代谢和慢性炎症的机制
基本信息
- 批准号:9897455
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-01-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:5&apos-AMP-activated protein kinaseAlcoholsAnimalsAnti-Retroviral AgentsApoptosisAstrocytesBehavioralBiogenesisBrainCarbohydratesCellsChronicClinicalConsequences of HIVCountryDevelopmentEnvironmentFatty acid glycerol estersGene ExpressionGenerationsGenesGlycoside HydrolasesHIVHIV InfectionsHIV-1HealthcareHealthcare SystemsHumanImmuneImmunologic Deficiency SyndromesImmunologic MarkersImmunologicsIn VitroInbred F344 RatsIndividualInfectionInflammationInflammation MediatorsInflammatory ResponseInterleukin-1MaintenanceMediatingMetabolismMitochondriaModelingMultiple AbnormalitiesNervous system structureNeurocognitive DeficitNeurologicNeuronal DysfunctionNicotinamide adenine dinucleotideNude RatsPPAR gammaPathologicPharmaceutical PreparationsPlasmidsProductionProtein KinaseProteinsRat TransgeneRattusRegulationRiskRoleSIRT1 geneSeriesSirtuinsSymptomsTNF geneTestingTranscription CoactivatorTransgenesTransgenic AnimalsTransgenic OrganismsTranslatingUnited States Department of Veterans AffairsVeteranscare providerschemical reactioncytokineeffective therapyexperienceimmune activationin vivoin vivo Modelinhibitor/antagonistinnovationnervous system developmentnovel strategiesresponse
项目摘要
The Veterans Healthcare Administration (VHA) treats more than 26,000 individuals with HIV infection, making it
the largest provider of care to HIV-infected individuals in the U.S. Neurological complications occur commonly in
HIV infection, with over 40% of individuals being at risk for developing HIV-related neurocognitive impairment
(NCI). Therefore, it is likely that a large number of Veterans experience symptoms related to NCI, which overall
responds poorly to treatment with antiretroviral drugs. Factors that underlie the development of NCI include
neuronal dysfunction due to enhanced production of proinflammatory cytokines (e.g., TNF- and IL-1) and other
inflammatory mediators that are secreted by HIV-infected cells in the brain.
Astrocytes make up the largest percentage of cells in the brain and, when infected by HIV-1, secrete
proinflammatory factors that can potentially have significant detrimental effects on the brain. In this proposal we
will examine the potential effects of nicotinamide adenine dinucleotide (NAD) metabolism and activation of the
glycohydrolase CD38, the energy sensing molecule 5' AMP-activated protein kinase (AMPK), peroxisome
proliferator-activated receptor gamma coactivator 1-α (PGC1α) and the sirtuin SIRT1 in suppressing nervous
system inflammation and other neuropathological abnormalities mediated by infection and activation of
astrocytes. For these studies we will utilize two transgenic rat models of HIV-1 infection. One is a well-
established model, developed on a wild-type F344 Fischer rat background (the HIV1Tg rat) and the other,
developed more recently, is on a on a nude Fisher rat background (the HIV1TgNu+ rat); which provides a model
of HIV infection in the presence of severe immunodeficiency.
The studies proposed in this Merit will be performed utilizing F344 and F344 nude (F344Nu+) rat primary
astrocytes transfected with a plasmid containing an insert that is identical to transgene that is present in the
transgenic rats as well as primary cells from the rats. Studies will be also performed in vivo using the animals.
The cells and animals will be treated with activators and inhibitors of NAD, CD38, AMPK and SIRT1 to determine
the effects of the agents on inflammatory response and neuropathological abnormalities that can occur. We
anticipate that information obtained utilizing these innovative models and approaches will lead to the
development of more effective treatments for HIV-related NCI in humans.
退伍军人医疗管理局(VHA)治疗了26,000多名艾滋病毒感染者,使其成为
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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WALTER ROYAL其他文献
WALTER ROYAL的其他文献
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{{ truncateString('WALTER ROYAL', 18)}}的其他基金
Nicotinic Acid Receptor Activation and Brain Proinflammatory Responses in HIV-1 Transgenic Rat
HIV-1 转基因大鼠烟酸受体激活和脑促炎反应
- 批准号:
10160861 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Mechanisms of NAD Metabolism and Chronic Inflammation in HIV-1 Transgenic Rat Models
HIV-1转基因大鼠模型中NAD代谢和慢性炎症的机制
- 批准号:
10083681 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Mechanisms of NAD Metabolism and Chronic Inflammation in HIV-1 Transgenic Rat Models
HIV-1转基因大鼠模型中NAD代谢和慢性炎症的机制
- 批准号:
10341091 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Mechanisms of NAD Metabolism and Chronic Inflammation in HIV-1 Transgenic Rat Models
HIV-1转基因大鼠模型中NAD代谢和慢性炎症的机制
- 批准号:
9242303 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Studies of Cigarette Smoke Exposure in an Animal Model of HIV-1 Infection
HIV-1 感染动物模型中香烟烟雾暴露的研究
- 批准号:
8624954 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Studies of Cigarette Smoke Exposure in an Animal Model of HIV-1 Infection
HIV-1 感染动物模型中香烟烟雾暴露的研究
- 批准号:
8735918 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Physical Telerahabilitation in Veterans with Multiple Sclerosis
患有多发性硬化症的退伍军人的身体远程康复
- 批准号:
8838115 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Physical Telerahabilitation in Veterans with Multiple Sclerosis
患有多发性硬化症的退伍军人的身体远程康复
- 批准号:
8499086 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Physical Telerahabilitation in Veterans with Multiple Sclerosis
患有多发性硬化症的退伍军人的身体远程康复
- 批准号:
8277575 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Opoid and Retinoid Interactions in the HIV-1 Transgenic Rat
HIV-1 转基因大鼠中阿片和类视黄醇的相互作用
- 批准号:
7229746 - 财政年份:2006
- 资助金额:
-- - 项目类别:
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