Methamphetamine and HIV interactions in the regulation of glial activation
甲基苯丙胺和艾滋病毒在神经胶质激活调节中的相互作用
基本信息
- 批准号:8669961
- 负责人:
- 金额:$ 47.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-07-01 至 2018-03-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS neuropathyAccountingAddressAffectAmphetamine UsersAstrocytesBehaviorBerylliumBindingBinding SitesBlood - brain barrier anatomyBrainCCR5 geneCREB1 geneCell LineCellsCharacteristicsCoculture TechniquesDataDisease ProgressionDopamineDoseElementsEquilibriumGenerationsGenesGenetic TranscriptionGlial Fibrillary Acidic ProteinHIVHIV InfectionsHIV-1ImmuneIn VitroInfectionInfiltrationInflammatoryInflammatory ResponseInvestigationMacacaMediatingMethamphetamineMicrogliaMusNeuraxisNeurogliaNeuronsNuclear TranslocationPathologyPathway interactionsPeptidesPharmaceutical PreparationsPhenotypePhosphorylationPlayPopulationPredispositionProcessRANTESReactive Oxygen SpeciesRegulationRegulatory ElementRoleSIVSignal InductionSignal TransductionSmall Interfering RNASymptomsSystemTATA BoxTranscription Factor AP-1Transgenic MiceUp-RegulationUrsidae FamilyViralViral Load resultVirusWestern Blottingbasebrain cellchemokinechemokine receptordrug of abusehigh risk behaviorimmune functionimmunocytochemistryin vivoinflammatory markerinflammatory modulationmacrophagemethamphetamine abuseneuropathologynovelpromoterpublic health relevancetranscription factor
项目摘要
DESCRIPTION (provided by applicant): HIV-1 exposure is associated with methamphetamine (Meth) abuse. These two factors synergize in aggravating neuroAIDS symptoms and disease progression. One of the important consequences of Meth on innate immune cells is to change the balance of reactive oxygen species (ROS) and induce inflammatory markers, such as CCR5 and RANTES. These changes are believed to be dopamine-dependent, but we have observed that both ROS and CCR5 can be induced in dopamine-free systems. Interestingly, ROS in the CNS can signal the increase of NFkB levels and phosphorylation, and directly induce activation of promoters of inflammatory molecules. On the other hand, HIV Tat, which also induces ROS, has been shown to potentiate glial activation and neuronal damage induced by Meth and other drugs of abuse. HIV Tat, but not Meth, increases several TATA-box binding components in macrophages in vitro, suggesting that it can have a modulatory effect on promoters of inflammatory molecules that bear a TATA-box promoter domain in the promoter. We hypothesize that transcriptional signaling triggered by Meth-induced ROS interact with a TATA-box-dependent modulatory mechanism in the presence of HIV Tat. We propose to explore the role of ROS-induced pathways in the upregulation of CCR5 and RANTES on astrocytes and microglia by Meth and Tat, aiming to identify the players in a dopamine-independent mechanism. We will also investigate whether the induction of TATA-box binding elements is at the basis of the ability of HIV Tat to modulate ROS and inflammatory markers in the CNS, affect immune cell infiltration and interfere with drug-related stereotypic behaviors. Using an original approach we expect to unveil a basic mechanism of interaction between HIV and Meth in the aggravation of CNS pathology, which will open a new line of investigation with a translational reach.
描述(由申请人提供):HIV-1暴露与甲基苯丙胺(Methe)滥用相关。这两个因素协同作用,加重neuroAIDS症状和疾病进展。Meth对先天免疫细胞的重要影响之一是改变活性氧(ROS)的平衡并诱导炎症标志物,如CCR 5和RANTES。这些变化被认为是多巴胺依赖性的,但我们已经观察到ROS和CCR 5都可以在无多巴胺系统中诱导。有趣的是,中枢神经系统中的ROS可以信号传导NF κ B水平和磷酸化的增加,并直接诱导炎症分子启动子的激活。另一方面,也诱导ROS的HIV达特已显示出增强由甲基苯丙胺和其他滥用药物诱导的神经胶质活化和神经元损伤。HIV达特而不是Meth在体外增加巨噬细胞中的几种TATA盒结合组分,表明它可以对启动子中携带TATA盒启动子结构域的炎性分子的启动子具有调节作用。我们推测,在HIV达特存在下,由Meth-induced ROS触发的转录信号与TATA盒依赖性调节机制相互作用。我们建议探索ROS诱导的通路在Meth和达特上调星形胶质细胞和小胶质细胞上的CCR 5和RANTES中的作用,旨在确定多巴胺非依赖性机制中的参与者。我们还将研究TATA盒结合元件的诱导是否是HIV达特调节CNS中ROS和炎症标志物、影响免疫细胞浸润和干扰药物相关刻板行为的能力的基础。使用原始的方法,我们希望揭示一个基本的机制,艾滋病毒和甲基之间的相互作用,在中枢神经系统病理的恶化,这将打开一个新的调查线与翻译的范围。
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 }}
Maria Cecilia Garibaldi Marcondes其他文献
Interleukin 18 and the brain: neuronal functions, neuronal survival and psycho-neuro-immunology during stress
白细胞介素 18 与大脑:应激期间的神经元功能、神经元存活和心理神经免疫学
- DOI:
10.1038/s41380-025-02951-z - 发表时间:
2025-03-22 - 期刊:
- 影响因子:10.100
- 作者:
Silvia Alboni;Fabio Tascedda;Akihito Uezato;Shuei Sugama;Zuxin Chen;Maria Cecilia Garibaldi Marcondes;Bruno Conti - 通讯作者:
Bruno Conti
Maria Cecilia Garibaldi Marcondes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('Maria Cecilia Garibaldi Marcondes', 18)}}的其他基金
Methamphetamine, HIV integration and latency in the brain
甲基苯丙胺、艾滋病毒整合和大脑潜伏期
- 批准号:
10814672 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Dopamine system as reporter of HIV status and inflammation in Meth abusers
多巴胺系统作为冰毒滥用者艾滋病毒状况和炎症的报告者
- 批准号:
10398692 - 财政年份:2021
- 资助金额:
$ 47.38万 - 项目类别:
Dopamine system as reporter of HIV status and inflammation in Meth abusers
多巴胺系统作为冰毒滥用者艾滋病毒状况和炎症的报告者
- 批准号:
10343776 - 财政年份:2019
- 资助金额:
$ 47.38万 - 项目类别:
Dopamine system as reporter of HIV status and inflammation in Meth abusers
多巴胺系统作为冰毒滥用者艾滋病毒状况和炎症的报告者
- 批准号:
10542737 - 财政年份:2019
- 资助金额:
$ 47.38万 - 项目类别:
Sirt-1-mediated regulation of NeuroAIDS
Sirt-1 介导的 NeuroAIDS 调节
- 批准号:
9552457 - 财政年份:2017
- 资助金额:
$ 47.38万 - 项目类别:
Methamphetamine and HIV interactions in the regulation of glial activation
甲基苯丙胺和艾滋病毒在神经胶质激活调节中的相互作用
- 批准号:
9450834 - 财政年份:2017
- 资助金额:
$ 47.38万 - 项目类别:
Sirt-1-mediated regulation of NeuroAIDS
Sirt-1 介导的 NeuroAIDS 调节
- 批准号:
9547742 - 财政年份:2017
- 资助金额:
$ 47.38万 - 项目类别:
Methamphetamine and HIV interactions in the regulation of glial activation
甲基苯丙胺和艾滋病毒在神经胶质激活调节中的相互作用
- 批准号:
9480123 - 财政年份:2017
- 资助金额:
$ 47.38万 - 项目类别:
Sirt-1-mediated regulation of NeuroAIDS
Sirt-1 介导的 NeuroAIDS 调节
- 批准号:
9267292 - 财政年份:2017
- 资助金额:
$ 47.38万 - 项目类别:
Methamphetamine and HIV interactions in the regulation of glial activation
甲基苯丙胺和艾滋病毒在神经胶质激活调节中的相互作用
- 批准号:
9031750 - 财政年份:2013
- 资助金额:
$ 47.38万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 47.38万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 47.38万 - 项目类别: