Interaction of HIV-1 Nef and glutamate homeostasis in the nucleus accumbens during cocaine addiction
可卡因成瘾期间伏隔核中 HIV-1 Nef 和谷氨酸稳态的相互作用
基本信息
- 批准号:10483802
- 负责人:
- 金额:$ 3.76万
- 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:2022-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAddressAstrocytesBehaviorBehavioral ModelBrainChronicCocaineCocaine DependenceCocaine UsersCocaine withdrawalConsumptionCorpus striatum structureCysteineCystineDataDevelopmentDisease ProgressionDown-RegulationDrug AddictionDrug usageElectrophysiology (science)EquilibriumExtinction (Psychology)Glial Fibrillary Acidic ProteinGlutamate TransporterGlutamatesHIVHIV InfectionsHIV diagnosisHIV-1HIV-associated neurocognitive disorderHealthHomeostasisHumanIllicit DrugsInfectionInflammationInjecting drug userKnowledgeLeadLongevityMeasurableMeasuresMediatingMissionModelingMolecularN-Methyl-D-Aspartate ReceptorsN-MethylaspartateNational Institute of Drug AbuseNerve DegenerationNeuraxisNeurogliaNeuronsNeuropathogenesisNeurotoxinsNeurotransmittersNucleus AccumbensPathologyPathway interactionsPatientsPersonsPharmaceutical PreparationsPlayPrimary Cell CulturesProductionProteinsPublic HealthRattusReceptor ActivationResearchRewardsRiskRisk FactorsRoleScienceSelf AdministrationSex BehaviorSliceSprague-Dawley RatsStructureSubstance Use DisorderSynaptic TransmissionUnited StatesUnited States National Institutes of HealthViralViral Load resultViral ProteinsVirus ReplicationWorkaddictionantiretroviral therapybasebeta cateninbrain tissuecell typecocaine exposurecocaine self-administrationcocaine usecomorbiditydrug seeking behaviorextracellularhigh risk behaviorillicit drug useimprovedin vivoinnovationinsightnef Proteinneuroinflammationneurophysiologyneurotoxicneurotoxicityneurotransmissionnew therapeutic targetnovelnovel therapeuticspreventprotein functiontransmission process
项目摘要
Summary
The recreational use of cocaine can lead to an addiction that increases the risk of acquiring the human
immunodeficiency virus (HIV) through high-risk behaviors such as an increase in unprotected sexual activity,
and a more rapid progression to AIDS. Approximately 33% of the 1.2 million people in the United States (US)
living with HIV use illicit substances, and approximately 1 in 10 new HIV diagnoses are attributed to injection
drug users every year. People living with HIV who take combination antiretroviral therapy (cART) and maintain
viral loads below detectable levels live a near-normal lifespan. However, despite the advances in efficacious
medication, there are still no medications that prevent the viral invasion to the central nervous system (CNS)
solidifying that the risk of developing HIV-1 associated neurocognitive disorders (HAND) has not decreased.
Therefore, to protect chronically infected people from the ravages of HIV-1 infection in the brain, particularly
when combined with substance use disorder (SUD), it is necessary to advance the understanding of the
intersection of HIV-1 and addiction to identify novel therapeutic targets.
Both cocaine and HIV proteins contribute to neuronal damage during disease progression through
dysregulation of glutamate homeostasis in the brain. It has been documented that as high as 19% of astrocytes
in the brains of patients with severe HAND are infected with HIV-1. Nef is one of the earliest expressed viral
proteins in approximately 1% of infected astrocytes. Even without measurable viral replication, Nef could
contribute to continued neuronal degeneration even in patients on cART. Extracellular glutamate is normally
taken up by astrocytes through a glutamate transporter (GLT-1) and exchanged for cysteine through the
cystine/glutamate exchanger. β -catenin, a dual function protein, regulates the expression of glutamate
transporters preventing neurotoxicity caused by excess NMDA receptor activation in neurons. However, cocaine
downregulates GLT-1 and the cystine/glutamate exchanger. During withdrawal of cocaine exposure, the
AMPA/NMDA ratio increases in the nucleus accumbens (NAc). The NAc is an important brain structure involved
in the development of cocaine addiction. The overall objective is to study the interaction between HIV-1 Nef and
cocaine related to glutamate homeostasis and drug-seeking behavior. The central hypothesis is that combined
cocaine exposure and astrocytic Nef expression will exacerbate glutamate excitation inducing
neurophysiological changes that strengthen synaptic transmission and reinforce the cocaine-seeking behavior.
To address this hypothesis, the team will develop the following two Specific Aims. Aim 1: Determine the impact
of HIV-1 Nef and cocaine on glutamatergic neurotransmission. Aim 2: Determine the impact of HIV-1 Nef on
cocaine-seeking behavior in rats. With the combination of in vivo self-administration, electrophysiology, and
molecular studies using brain tissue, the team will elucidate the role of HIV-1 Nef on cocaine-seeking and
consumption essential to developing new therapies to treat people with HIV and SUD.
总结
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jessalyn Gabrielle Pla Tenorio其他文献
Jessalyn Gabrielle Pla Tenorio的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jessalyn Gabrielle Pla Tenorio', 18)}}的其他基金
Interaction of HIV-1 Nef and glutamate homeostasis in the nucleus accumbens during cocaine addiction
可卡因成瘾期间伏隔核中 HIV-1 Nef 和谷氨酸稳态的相互作用
- 批准号:
10763810 - 财政年份:2022
- 资助金额:
$ 3.76万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 3.76万 - 项目类别:
Research Grant














{{item.name}}会员




