METH/HIV-1 Regulation of Astrocyte Responses: TAAR1 & Hyperthermia
METH/HIV-1 星形胶质细胞反应的调节:TAAR1
基本信息
- 批准号:8843718
- 负责人:
- 金额:$ 1.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-04-11 至 2015-05-17
- 项目状态:已结题
- 来源:
- 关键词:12 year oldAddressAgonistAminesAmphetaminesAstrocytesAttenuatedBehavioralBody TemperatureBrainCCL2 geneCalcium SignalingCentral Nervous System InfectionsClinicalClinical ResearchCognitiveComplicationContractsCyclic AMPDataDementiaDopamineDown-RegulationElderlyEpidemicFamilyForskolinG Protein-Coupled Receptor GenesG-Protein-Coupled ReceptorsGene Expression RegulationGenerationsGlutamatesGoalsHIVHIV-1Heat shock proteinsHeat-Shock Proteins 70Heat-Shock Proteins 90HourHumanHyperthermiaIL8 geneIndividualInduced HyperthermiaInfectionInflammationInflammatoryInterleukin-6InvestigationJudgmentLeadLibidoLightMeasuresMediatingMessenger RNAMethamphetamineMethamphetamine dependenceMitochondriaMolecularMorphologyNerve DegenerationNeuraxisNeurogliaNeurologicNeuronsOutcomeOxidative StressPathologyPatientsPharmaceutical PreparationsPhenethylaminesPhysiologic ThermoregulationPhysiologicalProcessProductionProteinsRNARNA InterferenceReactive Oxygen SpeciesRecoveryRegulationReportingRiskSeveritiesSignal PathwaySignal TransductionSignal Transduction PathwayTemperatureUnited StatesUp-Regulationastrogliosisattenuationchemokinecytokinedopamine transporterexcitotoxicityheat shock transcription factorhigh risk sexual behaviormethamphetamine abusemethamphetamine exposuremethamphetamine usemotor disorderneurocognitive disorderneuropsychologicalneurotoxicneurotoxicitynovelpsychostimulantpublic health relevancereceptorresearch studyresponseuptake
项目摘要
DESCRIPTION (provided by applicant): The goal of this proposal is to investigate METH-mediated activation of trace amine associated receptor 1 (TAAR1) and the downstream effects that lead to exacerbation of HIV-1 associated neurocognitive disorders in the context of METH-associated transient hyperthermia. As a psychostimulant, methamphetamine (METH) use results in strong, long lasting euphoric effects 1. During which, METH heightens the libido, impairs judgment and leads to risky sexual behavior ultimately increasing the risk of acquiring human immunodeficiency virus (HIV-1) 1, 2. The most severe form, HIV-associated dementia (HAD)3, is mediated by neurotoxic mechanisms including inflammation, glial activation, excitotoxicity, oxidative stress, and hyperthermia 1, 4-6. METH-induced hyperthermia peaks between 102-1030F/390C and brain temperature fluctuations between 10- 40C may contribute to neurodegenerative mechanisms 7, 8. In clinical studies METH dependence has an additive effect on HIV-1 associated neuropsychological deficits by exacerbating these common neuroinflammatory processes 1, 9. We show that astrocytes are sensitive to METH and postulate that trace amine associated receptor 1 (TAAR1) mediates METH-induced effects in astrocytes. As a G-protein coupled receptor activated by trace amines, TAAR1 initiates intracellular cyclic adenosine monophosphate (cAMP) signaling cascades leading to regulation of gene expression and cellular responses. TAAR1 was previously identified as an important neuronal receptor for METH action in dopamine transporter (DAT) regulation, glutaminergic signaling and thermoregulation 10-12. We propose that METH activates astrocyte TAAR1 leading to intracellular cAMP signaling further exacerbating astrocyte-mediated neurotoxicity in the context of HAND and METH- associated transient hyperthermia. We will address this hypothesis through the following aims: AIM 1 To investigate astrocyte TAAR1 regulation in response to METH/HIV-1ADA treatment and associated hyperthermia and AIM 2 To elucidate downstream signaling pathways of METH-induced astrocyte TAAR1 activation and associated transient hyperthermia thereby exacerbating HAND pathology. Completion of these studies will shed light on TAAR1 specific cAMP signaling in astrocytes during HIV-mediated neurodegeneration and METH-associated transient hyperthermia.
描述(由申请方提供):本提案的目的是研究在MET相关短暂性高热的背景下,MET介导的痕量胺相关受体1(TAAR 1)激活以及导致HIV-1相关神经认知障碍加重的下游效应。作为一种精神兴奋剂,甲基苯丙胺(METH)的使用导致强烈,持久的欣快效应1。在此期间,METH提高性欲,损害判断力,并导致危险的性行为,最终增加获得人类免疫缺陷病毒(HIV-1)的风险1,2。最严重的形式,HIV相关痴呆(HAD)3,由神经毒性机制介导,包括炎症、神经胶质活化、兴奋性毒性、氧化应激和高热1,4-6。METH诱导的高热峰值在102- 1030 F/390 C之间,脑温波动在10- 40 C之间,可能导致神经退行性机制7,8。在临床研究中,METH依赖通过加剧这些常见的神经炎症过程对HIV-1相关的神经心理缺陷产生叠加效应1,9。我们发现,星形胶质细胞是敏感的甲基和假设,微量胺相关受体1(TAAR 1)介导的甲基诱导的星形胶质细胞的影响。TAAR 1作为一种被微量胺激活的G蛋白偶联受体,启动细胞内环磷酸腺苷(cAMP)信号级联,从而调节基因表达和细胞反应。TAAR 1先前被鉴定为在多巴胺转运蛋白(DAT)调节、多巴胺能信号传导和体温调节中METH作用的重要神经元受体10-12。我们认为,METH激活星形胶质细胞TAAR 1,导致细胞内cAMP信号传导,进一步加剧了HAND和METH相关的短暂高热背景下星形胶质细胞介导的神经毒性。我们将通过以下目的来解决这个假设:目的1研究星形胶质细胞TAAR 1调节METH/HIV-1ADA治疗和相关的高热和目的2阐明下游信号通路的甲基诱导星形胶质细胞TAAR 1激活和相关的短暂高热,从而加剧手病理。这些研究的完成将揭示在HIV介导的神经变性和METH相关的短暂高热期间星形胶质细胞中TAAR 1特异性cAMP信号传导。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Methamphetamine Activates Trace Amine Associated Receptor 1 to Regulate Astrocyte Excitatory Amino Acid Transporter-2 via Differential CREB Phosphorylation During HIV-Associated Neurocognitive Disorders.
- DOI:10.3389/fneur.2020.593146
- 发表时间:2020
- 期刊:
- 影响因子:3.4
- 作者:Cisneros IE;Ghorpade A;Borgmann K
- 通讯作者:Borgmann K
{{
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 }}
Irma Cisneros其他文献
Irma Cisneros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('Irma Cisneros', 18)}}的其他基金
Targeting IDO in SARS-CoV2-induced Alzheimer's Disease progression
在 SARS-CoV2 诱导的阿尔茨海默病进展中靶向 IDO
- 批准号:
10670498 - 财政年份:2022
- 资助金额:
$ 1.01万 - 项目类别:
AIM(2)ing at the inflammasome: Impact of MAVS signaling in cocaine-and HIV-1 induced neuroinflammation
AIM(2)ing 作用于炎症小体:MAVS 信号传导对可卡因和 HIV-1 诱导的神经炎症的影响
- 批准号:
10371029 - 财政年份:2021
- 资助金额:
$ 1.01万 - 项目类别:
AIM(2)ing at the inflammasome: Impact of MAVS signaling in cocaine-and HIV-1 induced neuroinflammation
AIM(2)ing 作用于炎症小体:MAVS 信号传导对可卡因和 HIV-1 诱导的神经炎症的影响
- 批准号:
10574501 - 财政年份:2021
- 资助金额:
$ 1.01万 - 项目类别:
METH/HIV-1 Regulation of Astrocyte Responses: TAAR1 & Hyperthermia
METH/HIV-1 星形胶质细胞反应的调节:TAAR1
- 批准号:
8732418 - 财政年份:2014
- 资助金额:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 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:
$ 1.01万 - 项目类别:
Research Grant