Human/Animal Brain Chimera in drugs of abuse and HIV
滥用药物和艾滋病毒中的人/动物脑嵌合体
基本信息
- 批准号:10543385
- 负责人:
- 金额:$ 52.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-15 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AIDS populationAIDS/HIV problemAbstinenceAcquired Immunodeficiency SyndromeAddressAffectAnimal ModelAnimalsAreaAstrocytesAutopsyBiological AssayBiologyBloodBlood - brain barrier anatomyBrainCD34 geneCell modelCellsChimera organismCollaborationsDNA RepositoryDrug abuseEngraftmentEvolutionFunctional disorderGene Expression ProfileGenetic TranscriptionGenetic studyGenotypeGluesHIVHIV InfectionsHIV SeronegativityHIV SeropositivityHIV-associated neurocognitive disorderHomeostasisHumanImmunofluorescence ImmunologicImpaired cognitionIn SituIn VitroIndividualInfectionInflammatoryInflammatory ResponseInvadedKineticsKnowledgeLeadLearningLinkLymphocyteMETH abuserMediatingMediator of activation proteinMethamphetamineModelingMolecularMusNational Institute of Drug AbuseNational Institute of Neurological Disorders and StrokeNeurocognitive DeficitNeurodegenerative DisordersNeurogliaNeuronal InjuryNeuropathogenesisNeurotransmittersOrganPeripheralPeripheral Blood Mononuclear CellPersonsPharmaceutical PreparationsPhenotypePopulationResearchResourcesRisk FactorsRoleTechniquesTestingTimeTissuesUnited States National Institutes of HealthViralabuse victimantiretroviral therapyblood-brain barrier disruptionbrain cellbrain tissuecell repositorycohortcomorbiditydrug of abuseexperiencegenetic signaturegenome sequencinghuman modelhumanized mouseimmunoregulationin vitro activityin vivoinduced pluripotent stem cellinnovationmethamphetamine effectmethamphetamine usemethamphetamine usermouse modelneglectnerve stem cellneurotrophic factorneurotropicnewsnext generationnovelpsychostimulantrepairedresponsetool
项目摘要
Abstract: Drugs of abuse are a significant comorbidity among people living with HIV. Methamphetamine
(Meth), in particular, is a potent psychostimulant frequently abused in the HIV/AIDS population. Both HIV and
Meth are risk factors for cognitive decline even in the era of combination antiretroviral therapy (cART). The
mechanism(s) that drive and/or contribute to this cognitive decline, collectively known as HIV-Associated
Neurocognitive Impairment (HAND), are not entirely clear nor is the impact of Meth on HIV reservoir. Meth itself
enhances HIV replication. We will use two innovative humanized animal models to address the interface between
glial cells, Meth and HIV reservoir. huAstro/HuPBMC mice, generated by engraftment of IPSC-astrocytes into
NSG mice, can uniquely address the role of astrocytes as a reservoir for HIV and in HIV egress out of the brain
to peripheral organs (Aim 1) and define the effect of Meth with or without HIV on prototypical functions of
astrocyte and brain homeostasis (Aim 2). We focus on astrocytes because they constitute a significant resident
brain cell population and perform vital functions to maintain brain homeostasis. The HuCD34/NPC model (CD34
humanized mice engrafted with neuronal progenitor cells (NPCs) will be used to assess the role of Meth on HIV
evolution over time in the CNS and peripheral organs (Aim 3). Combining these two models with the resources
of the Translational Methamphetamine AIDS Research Center (TMARC) and the NIDA center for genetic studies
at Rutgers and cell repository (RUDCR) to reprogram lymphocytes from Meth/HIV donors to generate IPSC then
NPC and/or IPSC-astrocytes as targeted for in vitro and in vivo studies provides a powerful tool to address our
central hypothesis that Meth mediates a greater HIV reservoir in astrocytes and egress into peripheral organs
(Aim 1), dysregulate astrocytes to disrupt brain homeostasis (Aim 2), and promote s greater extent of viral
evolution within the CNS (Aim 3). Together, these studies are responsive to NIDA HIV research high priority
areas and will advance our knowledge regarding the role of drugs of abuse on HIV reservoir, evolution, and
neuropathogenesis to inform better strategies to uniquely address persistent HIV among the HIV positive drug
abusing population.
摘要:药物滥用是艾滋病毒感染者的重要合并症。甲基安非他命
项目成果
期刊论文数量(0)
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Lena Al-Harthi其他文献
Lena Al-Harthi的其他文献
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{{ truncateString('Lena Al-Harthi', 18)}}的其他基金
Human/Animal Brain Chimera in drugs of abuse and HIV
滥用药物和艾滋病毒中的人/动物脑嵌合体
- 批准号:
10683363 - 财政年份:2022
- 资助金额:
$ 52.86万 - 项目类别:
Dynamic interaction between HIV in the CNS and peripheral organs
HIV在中枢神经系统和周围器官中的动态相互作用
- 批准号:
10063582 - 财政年份:2019
- 资助金额:
$ 52.86万 - 项目类别:
Dynamic interaction between HIV in the CNS and peripheral organs
HIV在中枢神经系统和周围器官中的动态相互作用
- 批准号:
10524054 - 财政年份:2019
- 资助金额:
$ 52.86万 - 项目类别:
Dynamic interaction between HIV in the CNS and peripheral organs
HIV在中枢神经系统和周围器官中的动态相互作用
- 批准号:
10305639 - 财政年份:2019
- 资助金额:
$ 52.86万 - 项目类别:
Neuroimmune axis in HAND and HIV persistence in the brain
HAND 中的神经免疫轴和大脑中的 HIV 持续存在
- 批准号:
10088477 - 财政年份:2017
- 资助金额:
$ 52.86万 - 项目类别:
Neuroimmune axis in HAND and HIV persistence in the brain
HAND 中的神经免疫轴和大脑中的 HIV 持续存在
- 批准号:
9474682 - 财政年份:2017
- 资助金额:
$ 52.86万 - 项目类别:














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