Dopamine Exacerbates NeuroAIDS by Activation of Macrophage Dopaminergic System
多巴胺通过激活巨噬细胞多巴胺能系统加剧神经艾滋病
基本信息
- 批准号:8242055
- 负责人:
- 金额:$ 14.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-04-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS neuropathyAccelerationBrainCellsChemotaxisCocaineDataDevelopmentDopamineDopamine ReceptorDrug abuseEastern EuropeFar EastHIVHIV InfectionsHealthHumanImmuneIncidenceIndividualInfectionInflammationInflammatoryLifeMacaca mulattaMacrophage ActivationMediatingMethamphetamineNeuraxisNeurologicNeurotransmittersPathologyPharmaceutical PreparationsPopulationProductionProteinsResearchSIVSeveritiesSignal PathwaySiteSourceSystemVirusabstractingchemokinecytokinedopamine transporterdrug abuserdrug of abuseextracellularimmune functionmacrophagemethamphetamine abusenervous system disorderneuroinflammationneuropathologypandemic diseasereceptor-mediated signalingresponsesuccess
项目摘要
Abstract:
In regions of the world such as Eastern Europe and South-East Asia, the HIV pandemic is being driven by the
spread of HIV within drug-abusing populations. As HIV infected individuals live longer with the success of
CART, neurological complications are emerging as a significant health issue, particularly among HIV-infected
drug abusers. HIV infected individuals who abuse methamphetamine and cocaine show a significant increase
in the incidence and severity of neuropathology and in the development of HIV-associated neurological
disorders (HAND). The mechanism(s) leading to the acceleration HAND remain unclear; however, both
cocaine and methamphetamine act by increasing in extracellular levels of the neurotransmitter dopamine (DA)
within the central nervous system (CNS). Our findings demonstrate that dopamine increases HIV
replication in primary human macrophages, which are the primary target for HIV infection in the CNS.
Our research showed that this increase in macrophage HIV replication is due, at least in part, to the
infection of greater numbers of macrophages through the activation of a D2-like dopamine receptor.
Additionally, studies in simian immunodeficiency virus infected rhesus macaques showed that increased
extracellular dopamine enhances intracerebral HIV replication and exacerbates central nervous system
pathology. Together, these studies indicate that the effects of dopamine on HIV infection of macrophages
could be a common mechanism by which drug abuse exacerbates the development of HAND. Macrophages
are the primary targets and sources of HIV in the CNS, as well as a major immune responder and a major
source of cytokines and chemokines. Cytokines and chemokines increase neuroinflammation and mediate the
recruitment of uninfected macrophages to sites of inflammation, enabling the virus to spread to uninfected
macrophage populations. Our data show that dopamine not only increases HIV replication in macrophages, but
it activates dopamine receptor mediated signaling, modulates activation of chemotatic proteins and alters
cytokine production. These data suggest that drug-induced increases in dopamine would not only increase the
extent of HIV infection in the CNS, but could also enhance the spread of HIV to uninfected macrophages and
alter the macrophage response to infection. To characterize the mechanism(s) by which dopamine increases
HIV infection in macrophages and alters macrophage immune function, we will define dopamine mediated
changes in the HIV replication cycle in macrophages, examine alterations in macrophage chemotaxis and
production of inflammatory cytokines/chemokines, and characterize the DR signaling pathways in
macrophages mediating these functions. We hypothesize that dopamine increases HIV infection in
macrophages and alters macrophage functions through activation of dopamine receptors and
transporter, contributing to the exacerbated the development of HAND in HIV infected drug abusers.
文摘:
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)
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Peter Jesse Gaskill其他文献
Peter Jesse Gaskill的其他文献
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{{ truncateString('Peter Jesse Gaskill', 18)}}的其他基金
Defining molecular mechanisms by which stimulant evoked dopamine drives inflammation and neuronal dysfunction in neuroHIV
定义兴奋剂诱发多巴胺驱动神经艾滋病毒炎症和神经元功能障碍的分子机制
- 批准号:
10685160 - 财政年份:2023
- 资助金额:
$ 14.61万 - 项目类别:
Benzodiazepine mediated mechanisms of transcriptional semi-quiescence in discrete myeloid populations
苯二氮卓介导离散骨髓细胞群转录半静止机制
- 批准号:
10700122 - 财政年份:2022
- 资助金额:
$ 14.61万 - 项目类别:
Benzodiazepine mediated mechanisms of transcriptional semi-quiescence in discrete myeloid populations
苯二氮卓介导离散骨髓细胞群转录半静止机制
- 批准号:
10573380 - 财政年份:2022
- 资助金额:
$ 14.61万 - 项目类别:
DAT-Psychostimulant mediated dopamine release increases macrophage IL-1beta production through NF-kB activation and inflammasome priming
DAT 精神兴奋剂介导的多巴胺释放通过 NF-kB 激活和炎症小体引发增加巨噬细胞 IL-1β 的产生
- 批准号:
9978381 - 财政年份:2020
- 资助金额:
$ 14.61万 - 项目类别:
Mechanisms of dopamine mediated increase in HIV infection of macrophages
多巴胺介导的巨噬细胞HIV感染增加的机制
- 批准号:
9333313 - 财政年份:2015
- 资助金额:
$ 14.61万 - 项目类别:
Dopamine Exacerbates NeuroAIDS by Activation of Macrophage Dopaminergic System
多巴胺通过激活巨噬细胞多巴胺能系统加剧神经艾滋病
- 批准号:
8040993 - 财政年份:2010
- 资助金额:
$ 14.61万 - 项目类别:
Dopamine Exacerbates NeuroAIDS by Activation of Macrophage Dopaminergic System
多巴胺通过激活巨噬细胞多巴胺能系统加剧神经艾滋病
- 批准号:
8637953 - 财政年份:2010
- 资助金额:
$ 14.61万 - 项目类别:
Dopamine Exacerbates NeuroAIDS by Activation of Macrophage Dopaminergic System
多巴胺通过激活巨噬细胞多巴胺能系统加剧神经艾滋病
- 批准号:
9185430 - 财政年份:2010
- 资助金额:
$ 14.61万 - 项目类别:
Dopamine Exacerbates NeuroAIDS by Activation of Macrophage Dopaminergic System
多巴胺通过激活巨噬细胞多巴胺能系统加剧神经艾滋病
- 批准号:
8446427 - 财政年份:2010
- 资助金额:
$ 14.61万 - 项目类别:
Dopamine Exacerbates NeuroAIDS by Activation of Macrophage Dopaminergic System
多巴胺通过激活巨噬细胞多巴胺能系统加剧神经艾滋病
- 批准号:
7929994 - 财政年份:2010
- 资助金额:
$ 14.61万 - 项目类别:
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